About

Som Nanjappa is an Associate Professor of Immunology and an Associate Member of the Cancer Center at Illinois (CCIL) at the University of Illinois at Urbana-Champaign. His research interests focus on infectious immunology, particularly studying infections caused by opportunistic pathogens such as Blastomyces spp., Mycobacterium spp., and Toxoplasma spp., among others. His work is centered on understanding innate and adaptive immune responses to bacterial, fungal, and protozoan infections, with a specific emphasis on respiratory immune responses and the mechanisms involved in immunopathology during immunity to bacterial and fungal infections. Nanjappa has contributed to advancing knowledge in this field through his investigations into immune responses and immunopathology, and he has been involved in numerous research projects funded by agencies such as NIH and the Department of Defense. His academic background includes a Ph.D. from the University of Wisconsin-Madison and a DVM from the University of Agricultural Sciences in Bangalore, India. He has received multiple awards and grants recognizing his contributions to immunology and infectious disease research.

Research topics

• Immunology
• Biochemistry
• Biology
• Medicine
• Cancer research
• Microbiology
• Chromatography
• Chemistry
• Andrology
• Internal medicine
• Surgery

Selected publications

• OR29-06 Liver Receptor Homolog 1 (LRH-1) regulates myeloid immune cell functions, revealing a new approach to cancer therapy

  Journal of the Endocrine Society · 2025-10-01

  articleOpen access

  Abstract Disclosure: Y. Wang: None. N.A. Kulkarni: None. B. Duong: None. N. Krawczynska: None. S.V. Bendre: None. C.P. Schane: None. E. Weisser: None. L. Kockaya: None. Y. Fei: None. A. Das Gupta: None. H. Vidana Gamage: None. A.T. Nelson: None. S. He: None. S.G. Nanjappa: None. B.R. Gauthier: None. E.R. Nelson: None. Normal 0 false false false EN-US ZH-CN X-NONE /* Style Definitions */ table. MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Aptos",sans-serif; mso-ascii-font-family:Aptos; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Aptos; mso-hansi-theme-font:minor-latin; mso-fareast-language:ZH-CN;} Patients with high grade serous ovarian cancer or metastatic breast cancer have very poor 5-year survival rates. Furthermore, current standard of care therapies are often associated with significant side effects, including compromised immune systems. Thus, there is urgent need for new approaches to treating these diseases. Interestingly, we and others have implicated cholesterol in both of these cancers; elevated cholesterol being associated with poor prognosis, while patients on statins having an increased time to recurrence. Our previous work has identified myeloid immune cells as being very susceptible to perturbations in cholesterol homeostasis. The Liver Receptor Homolog 1 (LRH-1) is involved in regulating cholesterol catabolism. LRH-1 is expressed in myeloid immune cells, with relatively high expression in neutrophils. Neutrophils have been reported to have both pro- and anti-cancer functions. Therefore, we tested the hypothesis that LRH-1 regulates neutrophil functions important for cancer progression. We examined how LRH-1 activity influences various activities important for neutrophil function: migration, NETosis, phagocytosis and support of T cell activity. Adopting a pharmacologic approach, we found that LRH-1 decreased neutrophil migration toward cancer cells. LRH-1 was found to inhibit NETosis, a process where neutrophils extrude their DNA and associated proteins to form extracellular traps (NETs). LRH-1 activity in neutrophils also enhanced T cell expansion. Using murine models of mammary and ovarian cancer, we found that LRH-1 agonists reduced tumor growth, while an inverse agonist promoted tumor growth. NETosis has been described as a major driver of reemergence from breast cancer dormancy. Treatment of mice bearing dormant mammary cancer lesions with an LRH-1 inverse agonist significantly reduced the time to recurrence. Importantly, an agonist prolonged the time to recurrence. Thus, LRH-1 in neutrophils represents a novel target for the treatment of breast and ovarian cancer. Funding: National Cancer Institute (R01CA234025, R01CA288207, T32EB019944, T32GM136629, T32ES007326), Department of Defense (BCRP Era of Hope Award) Presentation: Monday, July 14, 2025

  PublisherOA PDFDOI

• Fungal vaccine-induced effector Tc17 cells need OXPHOS metabolism than glycolysis 2224

  The Journal of Immunology · 2025-11-01

  articleOpen access1st authorCorresponding

  Abstract Description Immunocompromised patients are highly susceptible to invasive fungal infections with high case fatality rates. We have shown that experimental attenuated live fungal vaccine-induced Tc17 cells are stable without plasticity and long-lived, necessary to mediate sterilizing immunity during CD4+ T cell deficiency. We observed effector Tc17 cells were metabolically highly active with high rate of proliferation and protein biosynthesis. We hypothesized that effector Tc17 cells adopt high energy-yielding metabolic pathways to form stable long-lived memory cells. The studies suggest that T cell expansion involves a metabolic shift from OXPHOS to glycolysis. Using a mouse model of attenuated live fungal vaccination, we found that glucose was necessary for effector Tc17 cells with variable dependency during the phases of expansion. Contrary to established dogma, we found that the effector Tc17 cells preferentially channelled the glucose to OXPHOS than glycolysis, correlated with higher mitochondrial mass and membrane potential. Inhibition of OXPHOS shrunk the Tc17 responses while sparing Tc1 responses. Our RNAseq data authenticated the preferential use of OXPHOS by effector Tc17 cells, unlike Tc1 cells. Collectively, the effector Tc17 cells predominantly utilize glucose for energy through OXPHOS rather than glycolysis and the apt adjuvants should bolster OXPHOS-mediated Tc17 expansion to enhance killed/subunit fungal vaccine efficacy tailored for immunocompromised patients. Funding Sources Supported by NIH/NIAID R01A153522. Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

  PublisherOA PDFDOI

• An ultrasensitive and modular platform to detect Siglec ligands and control immune cell function

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-12

  preprint

  Abstract Siglecs are immunomodulatory receptors that regulate immune cell function. A fundamental challenge in studying Siglec-ligand interactions is the low affinity of Siglecs for their ligands. Inspired by how nature uses multivalency, we developed Siglec-liposomes as a highly multivalent and versatile platform for detecting Siglec glycan ligands in which recombinant Siglecs were conjugated to liposomes using the SpyCatcher-SpyTag system. Siglec-liposomes offer tunable multivalency and a modular assembly, enabling presentation of different Siglecs on the same liposome. Using Siglec-liposomes, we profiled Siglec ligands on human leukocytes, revealing new insights into Siglec ligands. Moreover, Siglec-liposomes are in vivo compatible, where we demonstrated that Siglec-7-liposomes bind to the brain vasculature in a mucin-dependent manner. Given the abundance of Siglec ligands on T cells, we investigated whether Siglec-liposomes modulate T cell function and find that Siglec-7-liposomes increase T cell proliferation in a ST3Gal1-dependent and CD43-independent manner. Taken together, Siglec-liposomes are a versatile and sensitive tool for detecting Siglec ligands and immunomodulation.

  PublisherDOI

• ’Sialophorin is an essential element for fungal vaccine induced Tc17 cell differentiation and viability’ 2666

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Costimulatory molecules are integral for shaping T-cell responses and are attractive targets for T-cell modulation. Sialophorin (CD43) has disparate functions in hematopoietic cells and has been shown to negatively regulate antiviral CD8+ T cell responses. We investigated the mechanisms of essential role of CD43 for potentiating fungal vaccine responses. Using a mouse model of vaccine immunity, we demonstrated that CD43 significantly enhances Tc17 cell responses and fungal immunity. Our findings reveal that CD43 activates the Akt-mTOR-HIF1α signaling pathway, leading to increased RORγt expression in Tc17 cells without affecting their proliferation. Inhibition of Akt, mTORC1, or HIF1α resulted in diminished effector CD8+ T cell responses, while HIF1α stabilization augmented Tc17 responses in a CD43-dependent manner. Adoptive transfer experiments revealed the role of CD43 for effector CD8+ T cell survival by upregulating Bcl-2 levels and suppressing Caspase-3 activation. Notably, the Caspase-3 inhibitor treatment improved the survival of CD43-deficient Tc17 cells. These results offer a new perspective on CD43’s function, revealing its positive regulatory role in T-cell responses within the context of Tc17 cells and fungal immunity. Our study identifies CD43 as a potential target for enhancing vaccine efficacy and bolstering immunity against pulmonary fungal infections, offering new avenues for immune prophylactic/therapeutic interventions. Funding Sources This work is supported by NIH-NIAID 5R01AI153522 (to SGN). Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

  PublisherOA PDFDOI

• An ultrasensitive and modular platform to detect Siglec ligands and control immune cell function

  Science Advances · 2025-11-12 · 2 citations

  articleOpen access

  Siglecs are immunomodulatory receptors that regulate immune cell function. A fundamental challenge in studying Siglec-ligand interactions is the low affinity of Siglecs for their ligands. Inspired by how nature uses multivalency, we developed Siglec-liposomes as a highly multivalent and versatile platform for detecting Siglec glycan ligands in which recombinant Siglecs were conjugated to liposomes using the SpyCatcher-SpyTag system. Siglec-liposomes offer tunable multivalency and a modular assembly, enabling presentation of different Siglecs on the same liposome. Using Siglec-liposomes, we profiled Siglec ligands on human leukocytes, revealing distinct patterns of Siglec ligands. Moreover, Siglec-liposomes are in vivo compatible, where we demonstrated that Siglec-7-liposomes bind to the brain vasculature in a mucin domain-dependent manner. Given the abundance of Siglec ligands on T cells, we investigated whether Siglec-liposomes modulate T cell function and find that Siglec-7-liposomes increase T cell proliferation in an ST3Gal1-dependent and CD43-independent manner. Together, Siglec-liposomes are a versatile and sensitive tool for detecting Siglec ligands and immunomodulation.

  PublisherDOI

• Effector Tc17 cells resist shift from OXPHOS to aerobic glycolysis

  Frontiers in Immunology · 2025-05-16 · 3 citations

  articleOpen accessSenior authorCorresponding

  IL-17A-expressing lymphocytes, including Tc17 cells, are instrumental in immunity, immunopathology, and autoimmunity. We have previously shown that experimental attenuated live fungal vaccine-induced Tc17 cells are stable, long-lived without plasticity, and necessary to mediate sterilizing immunity during CD4 + T cell deficiency, which poses higher susceptibility to fungal infections. Cell metabolism is integral for T cell homeostasis but the metabolic adaptations of Tc17 cells are poorly defined. In this study, we hypothesized that effector Tc17 cells adopt high energy-yielding metabolic pathways to form stable, long-lived memory cells in vivo . Using a mouse model of attenuated fungal vaccination, we found that effector Tc17 cells were metabolically highly active with higher proliferation and protein synthesis than IFNγ + CD8 + T (Tc1) cells. Glucose was necessary for effector Tc17 cell expansion but with less dependency during the late expansion despite the active metabolism. Contrary to established dogma, we found that the effector Tc17 cells preferentially channeled the glucose to OXPHOS than glycolysis, which was correlated with higher mitochondrial mass and membrane potential. Inhibition of OXPHOS shrunk the Tc17 responses while sparing Tc1 cell responses. Tc17 cells actively relied on OXPHOS throughout the expansion period, resisting adaptation to aerobic glycolysis. Our data showed that the effector Tc17 cells predominantly utilize glucose for metabolism through OXPHOS rather than aerobic glycolysis. Our study has implications in vaccine design to enhance the efficacy and immunotherapeutics to modulate the immunity and autoimmunity.

  PublisherOA PDFDOI

• Fungal immunization potentiates CD4+ T cell-independent cDC2 responses for cross-presentation

  Frontiers in Immunology · 2025-05-26 · 1 citations

  articleOpen accessSenior authorCorresponding

  The incidence rates of fungal infections are increasing, especially in immunocompromised individuals without an FDA-approved vaccine. Accumulating evidence suggests that T cells are instrumental in providing fungal immunity. An apt stimulation and responses of dendritic cells are pivotal in inducing T-cell responses and vaccine success. Using a mouse model of fungal vaccination, we explored the dynamics, kinetics, activation, and antigen presentation of dendritic cell subsets to unravel the features of dendritic cell responses in the absence of CD4 + T cell help. The subcutaneous fungal vaccination induced more robust cDC2 responses than the cDC1 subset in draining lymph nodes. A single immunization with Blastomyces yeasts bolstered DC responses that peaked around day 5 before reverting to basal levels by day 15. The migratory cDC2 was the dominant DC subset, with higher numbers than all other DC subsets combined. Fungal vaccination augmented costimulatory molecules CD80 and CD86 without altering the levels of MHC molecules. Despite the higher fungal antigen uptake with migratory cDC2, the mean cross-presentation ability of all DC subsets was similar. Counterintuitively, deleting CD4 + T cells enhanced the DC responses, and CD4 + T cells were dispensable for conventional cross-presenting cDC1 responses. Collectively, our study shows that fungal vaccination selectively augmented cDC2 responses, and CD4 + T cells were dispensable for DC activation, antigen uptake, expression of costimulatory molecules, and cross-presentation. Our study provides novel insights into DC responses to an effective fungal vaccine for designing efficacious vaccines tailored for immunocompromised hosts.

  PublisherOA PDFDOI

• E3 ubiquitin ligase CBLB regulates innate immune responses and bacterial dissemination during nontuberculous mycobacteria infection

  Journal of Leukocyte Biology · 2024-01-25

  articleOpen accessSenior author

  Nontuberculous mycobacteria (NTM) are emerging opportunistic pathogens causing pulmonary infection to fatal disseminated disease. NTM infections are steadily increasing in children and adults, and immune-compromised individuals are at a greater risk of fatal infections. The NTM disease's adverse pathology and resistance to antibiotics have further worsened the therapeutic measures. Innate immune regulators are potential targets for therapeutics to NTM, especially in a T cell-suppressed population, and many ubiquitin ligases modulate pathogenesis and innate immunity during infections, including mycobacterial infections. Here, we investigated the role of an E3 ubiquitin ligase, Casitas B-lineage lymphoma proto-oncogene B (CBLB), in immunocompromised mouse models of NTM infection. We found that CBLB is essential to prevent bacterial growth and dissemination. Cblb deficiency debilitated natural killer cells, inflammatory monocytes, and macrophages in vivo. However, Cblb deficiency in macrophages did not wane its ability to inhibit bacterial growth or production of reactive oxygen species or interferon γ production by natural killer cells in vitro. CBLB restricted NTM growth and dissemination by promoting early granuloma formation in vivo. Our study shows that CBLB bolsters innate immune responses and helps prevent the dissemination of NTM during compromised T cell immunity.

  PublisherOA PDFDOI

• Advances in Dendritic Cell-Based Vaccines Against Respiratory Fungal Infections

  Preprints.org · 2024-07-26 · 2 citations

  preprintOpen accessSenior authorCorresponding

  Ever since the discovery of dendritic cells by Ralph Steinman and Zanvil Cohn in 1973, it is increasingly evident that dendritic cells are integral for adaptive immune responses, and there is an undeniable focus on them for vaccines development. Fungal infections, often thought in-nocuous, are becoming significant threats due to increased immunocompromised or im-mune-suppressed population and climate change. Further, the recent COVID-19 pandemic unraveled the wrath of fungal infections and devastating outcomes. Invasive fungal infections cause significant case fatality rates ranging from 20% to 90%. Regrettably, no licensed fungal vaccines exist, and there is an urgent need for preventive and therapeutic purposes. In this re-view, we discuss the ontogeny, subsets, tissue distribution, and functions of lung dendritic cells. In the latter part, we summarize and discuss the studies on the DC-based vaccines against pulmonary fungal infections. Finally, we highlight some emerging potential avenues that can be incorporated for DC-based vaccines against fungal infections.

  PublisherOA PDFDOI

• Lung Immunity to Fungal Infections by Macrophages: Mechanisms and Implications

  IntechOpen eBooks · 2024-10-29

  book-chapterOpen accessSenior author

  Pulmonary pathogenic fungi cause severe to fatal disseminated infections, especially in immunocompromised patients. Alveolar macrophages form an essential early innate cellular barrier implicated in immunity to pulmonary mycoses. The complex interactions of alveolar macrophages with pathogenic fungi lead to either effective clearance or disease progression. After sensing fungi through pattern-recognizing receptors, alveolar macrophage activation enhances phagocytic and non-phagocytic killing, secretion of cytokines/chemokines, and activation of other immune cells, including adaptive immune cells and neutrophils. Such an orchestrated response involves transcriptomic and metabolic adaptations by macrophages and epigenomic imprinting. Despite their high plasticity with the inflammatory cues, recent studies have shed light on their longevity and functional stability. Nevertheless, some pathogenic fungi have evolved strategies to evade or subvert alveolar macrophage function, leading to persistent and disseminated infections. Understanding the mechanisms of the macrophage-fungal interface helps develop a new line of immune therapeutics and mitigates the challenges of limited arsenals of antifungals.

  PublisherOA PDFDOI

Recent grants

• Immunity against fungal infections

  NIH · $2.3M · 2021–2026

• Role of GM-CSF+IL-17+ CD8+ T Cells in Respiratory Fungal Immunity

  NIH · $425k · 2016–2019

Frequent coauthors

• Srinivasu Mudalagiriyappa

  University of Illinois Urbana-Champaign

  16 shared

• Bruce S. Klein

  University of Wisconsin–Madison

  12 shared

• Jaishree Sharma

  10 shared

• Miranda D. Vieson

  Illinois College

  9 shared

• Marcel Wüthrich

  UW Health University Hospital

  9 shared

• M. Suresh

  7 shared

• Woosuk Choi

  University of Illinois Urbana-Champaign

  5 shared

• Lawrence Wang

  4 shared

Labs

• Nanjappa LabPI

Education

• PhD, Pathobiological Sciences

  University of Wisconsin Madison

  2008

• Bachelor of Veterinary Sciences and Animal Husbandry/DVM, Veterinary Sciences

  University of Agricultural Sciences

  2000

Awards & honors

• AAI Laboratory Travel Grant: American Association of Immunol…
• AAI Early Career Faculty Travel Grant: American Association…
• AAI Early Career Faculty Travel Grant: American Association…
• AAI Early Career Faculty Travel Grant: American Association…
• Innovation Award : American Lung Association, 2020