Plenary Speakers Matt Daugherty, Ph.D. (Virologist) University of California San Diego Professor, Department of Molecular Biology “Running with Scissors: Molecular and Evolutionary Arms Races Between Viral Proteases and Host Antiviral Immunity” June Round, Ph.D. (Immunologist) University of Utah Professor of Pathology (Microbiology and Immunology) “MicrobiotaͲImmune Interactions that Promote Health” Victor Torres, Ph.D. (Bacteriologist) St. Jude Children’s Research Hospital Chair, Department of HostͲMicrobe Interactions “Host Tropism and the Pathobiology of Staphylococcus aureus Infections” Twentieth Annual Frontiers in Immunobiology & Immunopathogenesis Symposium March 14, 2025
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Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 3 Tucson, Arizona: March 14, 2025 Agenda - Frontiers in Immunobiology & Immunopathogenesis Symposium Morning Activities BIO5 Institute, Room 103 7:30 - 8:25 AM Registration & Continental Breakfast 8:30 - 8:40 AM Welcome Announcements Michael Abecassis, MD, MBA Iovanna C. Lopez Dean, University of Arizona College of Medicine-Tucson Jennifer Barton, PhD Director, BIO5 Institute Janko Nikolich, MD, PhD Bowman Professor and Chair, Immunobiology Department Prabhu Arunachalam, PhD Assistant Professor, Immunobiology Department Session I: Immunology Moderators: Jennifer Uhrlaub and Colin Fields 8:40 – 9:30 AM Plenary Lecture, June Round, PhD Professor of Pathology (Microbiology and Immunology) University of Utah “Microbiota-Immune Interactions that Promote Health” 9:35 - 9:50 AM Lucas D’Souza, PhD “A genome-wide CRISPR screen reveals novel determinants of long-lived plasma cell secretory capacity”
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 4 Tucson, Arizona: March 14, 2025 9:55 - 10:10 AM Helena Batatinha, PhD “Exercise-Generated Cytokine-Induced Memory-Like NK Cells: A Novel Strategy for Boosting Immunotherapy Against Myeloid Leukemia” 10:15- 10:40 AM Henrique Borges da Silva, PhD “The eATP Receptor P2RX7 Promotes Optimal Progenitor Exhausted CD8+ T Cell Responses to Anti-PD1 Blockade” 10:45 – 11:15 AM BREAK, coffee available in Lobby Please visit our sponsors for a chance to win an iPad and other prizes 11:15- 11:30 AM Keila Espinoza, MS “Loss of Acid Ceramidase in Myeloid Cells Restores Sphingolipid Composition to Alleviate Chronic Colitis in IL10-Deficent Mice” The immunology session is sponsored by: Session II: Virology Moderators: Emily Vaslow and Rebekah Mokry 11:30 AM - 12:20 PM Plenary Lecture, Matthew Daugherty, PhD Professor, Department of Molecular Biology University School of California San Diego “Running with Scissors: Molecular and Evolutionary Arms Races Between Viral Proteases and Host Antiviral Immunity”
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 5 Tucson, Arizona: March 14, 2025 12:25 - 1:30 PM Lunch Sessions with Plenary Speakers Immunology Hot Topics BIO5 Institute, Room 103 Jennifer Uhrlaub and Colin Fields, Trainee Moderators Virology Hot Topics MRB, Room 102 Emily Vaslow and Rebekah Mokry, PhD, Trainee Moderators Bacteriology Hot Topics MRB, 2nd floor Lunchroom Yamil Sanchez-Rosario and Zoe Lyski, PhD, Trainee Moderators Afternoon Activities BIO5 Institute, Room 103 1:35 - 1:50 PM Isabelle Tobey, BS “HPV suppression of the cGAS/STING pathway” 1:55 – 2:10 PM Timothy White, PhD “HCMV pUL138 Drives Early Type I Interferon Signaling” 2:15 – 2:30 PM Rob Jackson, PhD “HPV16 Induces Subsite-Specific Differentiation Trajectories in 3D Organotypic Tonsillar Epithelium” The virology session is sponsored by:
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 6 Tucson, Arizona: March 14, 2025 2:30 – 2:50 PM BREAK, coffee available in Lobby Please visit our sponsors for a chance to win an iPad and other prizes Session III: Bacteriology Moderators: Yamil Sanchez-Rosario and Zoe Lyski 2:50 - 3:40 PM Plenary Lecture, Victor Torres, PhD Chair, Department of Host Microbe Interactions St. Jude Children’s Research Hospital “Host Tropism and the Pathobiology of Staphylococcus aureus Infections” 3:45 – 4:00 PM Vianney Mancilla, BS “The Emerging Role of Proteus mirabilis in Endometrial Cancer” 4:05 - 4:20 PM Nicole Jimenez, PhD “Genomic Characterization of Fannyhessea Reveals Insight into Pathogenic Mechanisms” Afternoon Activities MRB, Lobby and Room 102 4:20 - 5:30 PM Poster Session and Reception 5:30 PM Poster Awards & Prize Drawing The poster session is sponsored by:
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 7 Tucson, Arizona: March 14, 2025 Plenary Lecture Microbiota-Immune Interactions that Promote Health June Round, PhD University of Utah Colorectal cancer (CRC) is increasing globally, making identification of preventative measures necessary. Transplantation of the microbiota from CRC and non-CRC patients into mice demonstrates that non-diseased individuals possess organisms that reduce tumor formation and highlights a specific Bacteriodes species as protective. This Bacteriodes species is reduced in abundance in humans with CRC and proactive treatment with it slows tumor growth in mice. Surprisingly, NK cells, but not T-cells, are required for microbiota-mediated protection. CRC is recalcitrant to immunotherapies, however, addition of this Bacteriodes species restores response to α-CTLA-4 treatment in an NK-cell dependent manner. Further, induction of NK cell activity and reduced tumor growth is dependent on a specific B. uniformis capsular polysaccharide. Thus, healthy individuals possess tumor suppressor microbes that prevent cancer development and can be harnessed therapeutically.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 8 Tucson, Arizona: March 14, 2025 Plenary Lecture Running with Scissors: Molecular and Evolutionary Arms Races Between Viral Proteases and Host Antiviral Immunity Matthew Daugherty, PhD University of California San Diego Virally-encoded proteases are essential for the replication cycle of many viruses including SARSCoV-2, HIV, enteroviruses, and many more. At the same time, these proteases act to cleave host proteins at sequence specific sites. As a result, proteases and the immunity proteins they cleave are engaged in evolutionary arms races, where both virus and host can evolve to gain the upper hand in these important host-virus molecular conflicts. Our lab is developing computational and functional tools to discover new, rapidly evolving targets of viral proteases and determine the functional consequences of host target cleavage. This has allowed us to identify new immune functions that are antagonized in a host- and virus-specific manner. We have also discovered a novel innate mechanism for sensing viral infection via detection of the activity of the virallyencoded proteases. Together, these results indicate that viral proteases and the host proteins they cleave are critical players in the species specificity of viral infection and antiviral immunity.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 9 Tucson, Arizona: March 14, 2025 Plenary Lecture Host Tropism and the Pathobiology of Staphylococcus aureus Infections Victor Torres, PhD St. Jude Children’s Research Hospital Pathogens have evolved to be highly adapted to their natural hosts. Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300, for example, is a lineage responsible for the epidemic of skin and soft tissue infections (SSTIs) in humans. Due to its human tropism, the virulence mechanisms that contributed to USA300’s emergence as a major skin pathogen remain incompletely defined. Over the past several years, we have addressed this gap by developing a natural rodent model of S. aureus infection. In this seminar, I will present our recent discoveries on how S. aureus targets neutrophils to drive inflammatory pathology and enhance microbial survival within the infectious nidus in the skin. These findings provide new insights into key host-pathogen interactions in the skin and highlight the potential for developing much-needed anti-infectives.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 10 Tucson, Arizona: March 14, 2025 A Genome-Wide CRISPR Screen Reveals Novel Determinants of Long-Lived Plasma Cell Secretory Capacity Lucas D'Souza1, Jonathan Young2, Heather M Coffman3, Edward P Petrow Jr.4, Deepta Bhattacharya1 1 Department of Immunobiology, University of Arizona, Tucson, AZ, 2 Department of Otolaryngology, Sutter Health, Sacramento, CA, 3 Department of Otolaryngology, University of Arizona, Tucson, 4 Tucson Orthopedic Institute, Tucson, AZ Plasma cell subsets vary in their lifespans and ability to sustain humoral immunity. We conducted a genome-wide CRISPR-Cas9 screen in a myeloma cell line for factors that promote surface expression of CD98, a marker of longevity in primary mouse plasma cells. A large fraction of genes found to promote CD98 expression in this screen are involved in secretory and other vesicles, including many subunits of the V-type ATPase complex. Chemical inhibition or genetic ablation of V-type ATPases in myeloma cells reduced antibody secretion. Primary mouse and human long-lived plasma cells had greater numbers of acidified vesicles than did their short-lived counterparts, and this correlated with increased secretory capacity of IgM, IgG, and IgA. The screen also identified PI4KB, which promoted acidified vesicle numbers and secretory capacity, and Ddx3x, an ATP-dependent RNA helicase, the deletion of which reduced immunoglobulin secretion independently of vesicular acidification. Finally, we report a plasma-cell intrinsic function of the signaling adapter MYD88 in both antibody secretion and plasma cell survival in vivo. These data reveal novel regulators of plasma cell secretory capacity, including those that also promote lifespan.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 11 Tucson, Arizona: March 14, 2025 Exercise-Generated Cytokine-Induced Memory-Like NK Cells: A Novel Strategy for Boosting Immunotherapy Against Myeloid Leukemia Helena Batatinha1, Angella Venezuela1, Dimitrios Filioglou2, Phelipe Varela3, Geovana Leite2, Emmanuel Katsanis2, Richard J Simpson1 1 School of Nutritional Sciences and Wellness, 2 Department of Pediatrics, University of Arizona, Tucson, AZ, 3 Universidade Federal do Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil Overnight activation of NK cells with IL-12, IL-18, and IL-15 generates Cytokine-Induced Memory-Like (CIML) NK cells, a promising immunotherapy product with enhanced anti-tumor activity, prolonged proliferation, and improved in vivo persistence. Clinical trials evaluating CIML NK cells in high-risk leukemia patients have shown encouraging results. However, challenges remain, including prolonged cytotoxicity and sustained remission. We recently demonstrated that a single bout of exercise induces a fivefold increase in circulating NK cells, which also exhibit upregulated gene sets and surface proteins associated with anti-tumor activity. Here, we propose leveraging exercise-mobilized NK cells to enhance the function of CIML NK cells. Ten healthy subjects completed a 20-minute bout of graded cycling exercise, with blood samples collected at rest and during the final two minutes of exercise. NK cells were isolated from resting (NK) and exercise (NK-X) mobilized PBMCs and stimulated overnight with IL-15 only (control) or IL-12, IL-18, and IL-15 to generate CIML NK cells. The resulting cells were tested for in vitro cytotoxicity against K562 (CML) and Kasumi-1 (AML) cells lines and injected into K562 leukemia-bearing NSG-IL15 mice to assess in vivo persistence and anti-tumor activity. CIML NK cells derived from exercise-mobilized NK cells (CIML NK-X) exhibited enhanced in vitro cytotoxicity against both leukemia cell lines, supported by increased IFNγ production and degranulation. Notably, NK-X displayed comparable cytotoxicity to standard CIML NK cells, indicating that exercise alone enhances NK cell cytotoxic potential. Triple cytokine stimulation upregulated the inhibitory receptor NKG2A; however, CIML NK-X demonstrated reduced NKG2A expression. In leukemia-bearing mice, CIML NK-X treatment prolonged NK cell engraftment, delayed tumor progression, and extended survival compared to standard CIML NK treatment. Our findings suggest that combining targeted cytokine activation with exercise-induced NK cell mobilization generates functionally superior CIML NK cells with enhanced in vitro and in vivo cytotoxicity against myeloid leukemia cells. Exercise may, therefore, be a promising strategy for improving immunotherapy outcomes in high-risk leukemia relapse.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 12 Tucson, Arizona: March 14, 2025 The eATP Receptor P2RX7 Promotes Optimal Progenitor Exhausted CD8+ T Cell Responses to Anti-PD1 Blockade Henrique Borges da Silva, Caio Loureiro Salgado Mayo Clinic, Scottsdale, AZ Persistent exposure to antigens and immunosuppressive signals in tumors or chronic infections drives CD8+ T cell exhaustion (Tex), a programmed state of T cell dysfunction. While efforts have been made to combat Tex through immunotherapies, they often fail to induce lasting protective effects. Exhausted CD8+ T cells consist of various subsets with distinct transcriptional, functional, and metabolic features. Among these subsets, progenitor exhausted CD8+ T cells (Tprog) are important: they are metabolically quiescent, retain stemness capacity and respond better to checkpoint blockade therapy (e.g., anti-PD1). Here, we report that, in response to solid tumors (melanoma, breast cancer, liver cancer) and chronic viral infection (LCMV Clone 13), P2RX7 is crucial for the establishment of Tprog cells and protection from tumor growth or viremia. P2RX7- KO CD8+ T cells had decreased numbers of Tprog cells. Mechanistically, we found, using SCENITH analysis, that P2RX7-KO Tprog cells lose metabolic quiescence, displaying increased glycolytic function and loss of mitochondrial respiration dependence. Our meta-analyses of gene (scRNAseq) and protein (LegendScreen assay) expression suggest that P2RX7-KO Tprog cells undergo abnormal exhaustion differentiation paths, and express reduced levels of integrin beta-1 (ITGB1), a molecule associated with lymphoid residency of Tprog cells. Finally, we found that P2RX7 is crucial for exhausted CD8+ T cells to respond to anti-PD1 in vivo. These data open the possibility of using P2RX7 agonism to boost the efficacy of existing checkpoint blockade immunotherapies aimed to revitalize CD8+ T cell responses against solid tumors.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 13 Tucson, Arizona: March 14, 2025 Loss of Acid Ceramidase in Myeloid Cells Restores Sphingolipid Composition to Alleviate Chronic Colitis in IL10-Deficent Mice Keila Espinoza1, Marilyn Marron2, Brandon Dahl2, Cameron Beard2,3, Justin Snider2,4, Ashley Snider2,4 1 Physiological Sciences GIDP, 2 School of Nutritional Science and Wellness, 3 University of Arizona College of Medicine, 4 University of Arizona Caner Center, University of Arizona, Tucson, AZ Inflammatory bowel disease (IBD) is a chronic disease that increases the risk of colorectal cancer (CRC). Perturbations to sphingolipid metabolism are well implicated in IBD and CRC. Acid ceramidase (AC) is highly expressed in macrophages in patients with IBD and CRC. AC degrades ceramide and can lead to the generation of the bioactive lipid sphingosine-1-phosphate (S1P). Our lab has shown that the conditional loss of AC in myeloid cells (ACMYE) reduced local and systemic inflammation in mice with acute DSS-induced colitis. We then investigated loss of AC in IL10 deficient mice, a physiologically relevant model which closely recapitulates human disease. ACMYEIL10-/- and ACfl/flIL10-/- mice were generated and collected at 8 and 24 weeks of age for assessment of early and late-stage disease, respectively. ACMYEIL10-/- mice were protected from spleen enlargement and colon shortening at 24 weeks of age. Ceramides and sphingomyelins (SMs) were elevated in ACMYEIL10-/- mice as measured by LC-MS/MS. Moreover, long chain ceramides (C14, C16, C18:1) were increased in ACMYEIL10-/- mice at 8 or 24 weeks of age. Interestingly lyso-SM, which can be generated by AC, was reduced in ACMYEIL10-/- mice. Sphingoid bases, dhS1P, and S1P were additionally reduced in ACMYEIL10-/- mice. Protein and mRNA expression of inflammatory markers were significantly increased as ACfl/flIL10-/- mice aged to 24 weeks, yet remained unchanged in ACMYEIL10-/- mice. FACS analysis revealed reduced infiltration of neutrophils and TypeM1 macrophages in the colons of ACMYEIL10-/- mice. Interestingly, Th1 andTh17 effector T cell populations were reduced in ACMYEIL10-/- mice across various tissues. Collectively these data suggest that loss of AC in myeloid cells protects from chronic inflammation and may indicate a role for AC in mediating cell-to-cell crosstalk. Our findings indicate that AC may be a promising therapeutic target as a novel treatment of IBD and reducing the risk of CRC. This work is supported by the National Institute of Diabetes and Digestive and Kidney Diseases R01 DK132079 (AJS).
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 14 Tucson, Arizona: March 14, 2025 HPV Suppression of the cGAS/STING Pathway Isabelle Tobey1, David Kosanke2, Kelly King3, Samuel Campos1,2,3,4, Koenraad Van Doorslaer1,3,4,5 1 Cancer Biology GIDP, 2 Department of Molecular and Cell Biology, 3 Department of Immunobiology, 4 BIO5 Institute, 5 Genetics GIDP, University of Arizona, Tucson, AZ The cGAS/STING pathway is an important pathway for sensing and responding to foreign DNA or damaged host DNA. Given that HPV has been found to induce genomic DNA damage and potentially release viral genomes into the cytosol where it may be sensed by cGAS, it tracks that HPV has been found to downregulate many parts of this pathway. Although many studies have described the effects of HPV oncogene over expression on aspects of cGAS/STING pathway, our understanding of how HPV modulates cGAS/STING during the early viral life cycle is incomplete. Using HPV18 immortalized primary keratinocytes and patient-matched HPV negative controls, we examined pathway activation in the hours following dsDNA stimulation. Across three biological donors, we found that HPV positive and negative cells have the same level of cGAS protein and yet HPV positive cells produce more cGAMP, both at baseline and following DNAstimulation, than their corresponding HPV negative cells. Despite this, HPV positive cells suppressed peak phospho-STING and phospho-IRF3 levels. Additionally, we ran bulk RNA sequencing to examine HPV-mediated changes of downstream interferon-stimulated genes. We found that HPV modulates many DNA-responsive genes by decreasing baseline and/or suppressing activation. We also identified a subset of DNA-responsive genes in which HPV increases or sustains activation. Finally, we examined which of the HPV oncogenes were increasing cGAMP production as well as suppressing STING activation. We found that both E6 and E7 are playing a role in driving cGAMP production and blunting STING responses in HPV positive cells. Our results carefully map cGAS/STING pathway activation kinetics in HPV positive and negative cells and indicate that the HPV oncogenes work together to increase cGAMP production while suppressing STING activation and attenuating downstream signals.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 15 Tucson, Arizona: March 14, 2025 HCMV pUL138 Drives Early Type I Interferon Signaling Timothy White1, Dimitri Koliopoulos1, Mamata Savanagouder1, Emily Jamboretz1, Felicia Goodrum1,2 1 Department of Immunobiology, 2 BIO5 Institute, University of Arizona, Tucson, AZ Human cytomegalovirus (HCMV) initiates infection in a wide range of cell types prior to establishing latency in CD34+ hematopoietic progenitor cells (HPCs). During this acute infection, innate immune responses, including the release of type I interferons, are crucial in restricting viral replication. In fibroblasts, a type I interferon response occurs within hours of infection, peaking at 6-9 hours post infection (hpi) and resulting in translocation of phosphorylated STAT1 to the cell nucleus to initiate transcription of antiviral effectors. Counterintuitively, although most viral proteins work to suppress innate immune responses, the HCMV protein pUL138 enhances STAT1 signaling. Previous research from our lab demonstrated that pUL138 sustains STAT1 phosphorylation at 48-72 hpi through an interaction with the deubiquitylating complex, UAF1/USP1. In this study, we investigate the role of pUL138 at earlier time points in infection. Wild-type (WT) HCMV induces strong phosphorylated STAT1 (pSTAT1) by 6 hpi. UL138-null virus (UL138STOP) infection, in contrast, exhibits lower and delayed pSTAT1 signaling relative to the WT infection. Immunofluorescence imaging reveals that pSTAT1 is found primarily in the nuclei of infected cells, not bystanders, indicating autocrine, rather than paracrine, signaling. More than 90% of cells infected with WT HCMV show pSTAT1 colocalizing with viral immediate early proteins (IEs) by 6 hpi, while less than 15% of IE-positive cells show colocalized pSTAT1 during UL138STOP infection. A virus expressing a defective UL138 which is unable to bind the interactors UAF1 and USP1 nevertheless triggers a pSTAT1 response comparable to WT HCMV, indicating a UAF1-independent mechanism. The observed STAT1 phosphorylation is dependent on interferon alpha receptor (IFNAR) signaling, and knockdown of IFNAR1 or the cofactor STAT2 result in diminished pSTAT1. Collectively, these results provide new insight into the role of pUL138 in enhancing immune responses during early HCMV infection, which may be a mechanism for driving a latency program.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 16 Tucson, Arizona: March 14, 2025 HPV16 Induces Subsite-Specific Differentiation Trajectories in 3D Organotypic Tonsillar Epithelium Rob Jackson1 , Christina Arnoldy1 , Koenraad Van Doorslaer1,2,3,4,5 1 Department of Immunobiology, 2 BIO5 Institute, 3 University of Arizona Cancer Center, 4 Cancer Biology GIDP, 5 Genetics GIDP, University of Arizona, Tucson, AZ The rate of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) has surpassed cervical cancers and is considered an epidemic in the US. Nearly all HPV(+) OPSCCs are caused by HPV16 and most arise in the tonsils. Importantly, it is a nonproductive outcome for this virus to transform host epithelial cells. In the natural course of HPV infection, a productive viral lifecycle yields infectious viral particles. It is thought that HPV delays but still requires normal epithelial differentiation to complete its lifecycle. However, the interplay between tonsillar differentiation and the spatiotemporal regulation of HPV16’s lifecycle is poorly understood. Our research aims to decipher interactions between HPV16and tonsillar differentiation programs: including the outer surface and crypt. Clinical data suggest that tonsil crypts are preferential sites of transformation, while outer surfaces are rarely the origin sites of HPV16(+) OPSCCs. Since HPVs infect stratified tissue, we differentiated primary tonsillar surface and crypt cells and extrachromosomal HPV16(+) clones in 3D organotypic rafts. We found subsite differences: viral productivity marker E4 is induced to a greater extent in surface vs crypt cells. We performed scRNA-seq on rafts to determine to what extent HPV16 alters epithelial subsets across the differentiation gradient. We found that transcriptional variation was driven by transitions from basal to superficial cells, as expected, and that HPV16 expanded the pool of cycling cells. Using pseudotime trajectories to capture continuous transitions we found that HPV16 shifted the differentiation gradient of tonsil cells in a subsite-dependent manner and that HPV16 induced a unique alternate branch of differentiating cells in the surface only: candidate cells that can support productive viral amplification. These tonsil surface cells are enriched by HPV16 and include a transcriptional signature of oxidative phosphorylation genes. This indicates that HPV16 drives distinct reprogramming of terminal tonsil cell differentiation and that intrinsic epithelial subsite differences impact productive capability. Overall, these findings help address the molecular basis of HPV16’s productivity vs transformation in tonsils.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 17 Tucson, Arizona: March 14, 2025 The Emerging Role of Proteus mirabilis in Endometrial Cancer Vianney Mancilla1, Nicole R Jimenez2, Holly Chatenoud3, Pawel Laniewski1, Melissa M Herbst-Kralovetz1,2 1 Department of Basic Medical Sciences, 2 Department of Obstetrics and Gynecology, University of Arizona, Phoenix, AZ, 3 Department of Life Sciences, University of Bath, Bath, UK Endometrial cancer (EC) is the most common gynecological cancer worldwide and the 4th most common cancer in women in the U.S. The microbiome may be a key target for understanding EC etiology. Disruption of the cervical barrier may cause pathogenic microbes to ascend into the upper reproductive tract and modulate the endometrial microenvironment that promotes cancer. Proteus mirabilis is a motile rectal pathogen that causes urinary tract infections and is also linked to endometritis. We hypothesized that women with EC would exhibit higher proportions of P. mirabilis with community networks of endometritis-associated pathogens. We collected endometrial microbiome samples (N=185) from women with EC (n=59) or benign gynecologic conditions (n=101). 16S rRNA gene sequences were analyzed with QIIME 2, Microbiome Analyst, and Fisher's exact test. Glycerol endometrial swab samples (n=30) were evaluated for bacterial growth. Cervicovaginal lavages were utilized to evaluate metabolites and immune markers. P. mirabilis was identified in 62/185 samples based on 16S rRNA data, with an abundance range of 1.0-8.0%. P. mirabilis was more frequently detected (13.6%) in patients with nonendometroid EC (p=0.03) and grade 2-3 tumors (p=0.06). Profiles of patients with endometrial P. mirabilis exhibited higher species richness (p<0.0001). Beta-diversity (p=0.004) was significantly distinct between groups with presence and absence of endometrial P.mirabilis. P. mirabilis significantly co-occurred with 17 taxa, top taxa including Porphyromonas, and Burkholderiales which are associated with endometrial cancer and endometritis. CVL profiling observed increased abundance of P. mirabilis with elevated inflammatory markers of CYFRA 21- 1, CD40, trimethylamine N-oxide, and six xenobiotics related to drug metabolism. We cultivated P. mirabilis from 50% of glycerol samples with P. mirabilis identified by sequencing, which in microaerophilic environments outcompeted organisms via its signature swarming effect. However, no P. mirabilis was isolated in strict anaerobic conditions. These findings expand knowledge on the emerging mechanism of P.mirablis in the tumor microenvironment associated with EC advancement, facilitating future investigation into potential therapeutic strategies for EC.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 18 Tucson, Arizona: March 14, 2025 Genomic Characterization of Fannyhessea Reveals Insight into Pathogenic Mechanisms Nicole R Jimenez1, Pawel Laniewski2, Melissa M Herbst-Kralovetz2 1 Department of Obstetrics and Gynecology, 2 Department of Basic Medical Sciences University of Arizona, Phoenix, AZ, Fannyhessea vaginae is linked to bacterial vaginosis, HPV acquisition, and cervical cancer. Metagenomic studies have indicated sizeable microbial diversity within the cervicovaginal microbiome. We hypothesize that F. vaginae has the potential for taxonomic reclassification, and genomic diversity within Fannyhessea may indicate unique pathogenic capabilities that contribute to HPV persistence/progression to cancer. Selection of 19 public genomes in the Bacterial and Viral Bioinformatics Resource Center were utilized. Two additional F. vaginae strains from public repositories or isolated in-house underwent whole genome sequencing, assembly, and annotation. Comparative genomic analyses included phylogenetics, protein alignment, and proteomic comparison. Phylogenetic analysis of orthologs revealed three distinct clades within the Fannyhessea: Clade 1 (Fannyhessea vaginae), Clade2 (Fannyhessea species type 2), and Clade 3 (Fannyhessea massiliense). 16S rRNA-based phylogenetic gene tree of 26 sequences revealed a similar trend. Protein alignment with F. vaginae representative strain NCTC13935 indicated average percent identities with Clade 1 (98.0%). Lower percentages were reported for Clade 2 (64.7%) and Clade 3 (64.9%), indicating high dissimilarity. On average, Fannyhessea spp. had 1.44 Mb genome size, 45.3%GC content, and 1318 coding sequences. Clade 1 had a low GC at 43.8% and the lowest CDS at 1241, suggesting Clade 1 may be more host-adapted. Protein comparison identified 334 proteins shared amongst Fannyhessea. Clade 1 had 111 unique proteins, including DegV, related to lipid involvement in extracellular vesicles. Clade 2 had 44 unique proteins, including proteins involved in biogenic amine metabolism. While Clade 3 had 317 unique proteins, including proteins involved in hyaluronic acid degradation and galactose/maltose metabolism, compounds abundant in the cervicovaginal microenvironment. Collectively, our findings provide preliminary evidence that F. vaginae is a candidate for separation into three genomospecies. Each species has significant differences in genomic and putative virulence capability. These differences may contribute to the oncogenic potential of Fannyhessea, warranting host-microbe investigation into these new species.
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 19 Tucson, Arizona: March 14, 2025 Poster Titles Poster Author Abstract Title 1 Mahi Rohilla Investigating Copper and Iron Binding in Streptococcus pneumoniae Proteins SP_1032 and SP_1872 2 Fadi Sayegh Carbon Source Utilized by Pneumococcus Dictates Clearance by Macrophages 3 Evy Nguyen Regulatory Mechanisms of Neisseria subflava Capsule Polysaccharide Biosynthesis 4 Sloane McVicker Investigating Regulation and Function of Putative Surface Lipoprotein Assembly Modulators (Slam) in Commensal Neisseria 5 Treena Teh Unraveling the Role of Lactobacillus iners in HPV Infection and Cervical Carcinogenesis: A Review in Asian Cohorts 6 Anika Arias S. anginosus Promotes Inflammatory Responses from Macrophages by Activating the NLRP3 Inflammasome 7 Anita Garwolinska Targeted Lipidomics Unveils Complex Lipids in Cervicovaginal Environment as Diagnostic and Prognostic Biomarkers for Endometrial Cancer 8 Esther Qiu Does BACE1 Inhibition Impair Recovery from Stroke in Mouse Models of Alzheimer’s Disease? 9 Hariti Soni Generating MHCII and MHCI Knockout M12 Cell Lines Using CRISPR-Cas9 10 London McDougal Exercise-Mobilized Donor Lymphocyte Infusions Enhanced with Cytokines Have Increased Polyfunctionality and Anti-Leukemia Activity 11 Natasha Aitchison Global Metabolic and Lipidomic Profiling of Cervicovaginal Lavages for Non-Invasive Cervical Cancer Detection 12 Randy Chou Exercise-Mobilized Lymphocytes Have Enhanced Cytotoxicity Against Multiple Myeloma in Combination with CD47 and CD38 Targeted Monoclonal Antibody 13 Omar Al-Ali Development of a 5MCAR-Based Strategy to Deorphanize TCRs 14 Abigail LoCascio Engineering Biomimetic Stimulators to Bind to HER2+ Cells and Activate T Cell Defenses 15 Sydney Verdugo Toll-Like Receptor Adaptor WDFY1 Provides Protection Against Intestinal Inflammation 16 Grace McKenzie Daratumumab Augments Exercise Expanded γδ T-cells Cytotoxic Function against Multiple Myeloma 17 Andrew Khalil Systems Biological Assessment of Chronic Inflammation in Aging 18 Alma Banuelos The eATP-Exporting Channel Pannexin-1 Promotes CD8+ T Cell Responses to Colorectal Cancer 19 Briana Byrne An Evaluation of Immunometabolic Contributions to the Cervicovaginal Environment in Benign Gynecological Conditions 20 Jaden Todd-Nelson Characterizing the Role of Ctr2 in Latent Toxoplasma gondii Infection 21 Christina Arnoldy HPV RNA Modifications Change with Host Keratinocyte Differentiation 22 David Kosanke Expressing Recombinant Human Papillomavirus Genomes with Selectable Traits In Tonsillar Keratinocytes 23 Ashlin Schaefbauer Differential Roles of Gamma Secretase Complexes and p120 Catenin in Human Papillomavirus Infection 24 Kelly King HPV18 Alternative Splicing is Regulated by PRMT1-Dependent m6A Methylation of Viral mRNA 25 Zachary Williamson Investigating the Role of Potassium Channels in HPV16 Minor Capsid Protein spanning
Frontiers in Immunobiology & Immunopathogenesis Symposium 2025 / 20 Tucson, Arizona: March 14, 2025 Organizing Committee Kate Rhodes, PhD (chair) Prabhu Arunachalam, PhD Colin Fields Rebekah Mokry, PhD Yamil Sanchez-Rosario Bao Thai Jennifer Uhrlaub, MS Emily Vaslow Zoe Lyski, PhD Polly Haffner Kristen Lynch Tammie Rippberger Further acknowledgement is made for the grateful assistance of: Edgar Mendoza - BioCOM Poster Judges Roslyn Dermody, PhD Lucas D’Souza, PhD Rob Jackson, PhD Nicole Jimenez, PhD Franziska Kuehner, PhD Pierce Longmire, PhD Rithy Meas, PhD Maria Rendon, PhD Chandrasekarana Sambamurthy, PhD Sandip Sonar, PhD Jennifer Uhrlaub, MS Cover photos courtesy of: UAHS BioCOM, Images provided by Colin Fields