Microbiology and Immunology Discipline

Dr. Vijay completed his DVM from Kerala Agricultural University, India, in 2008. He then joined Bucknell University in Pennsylvania for his Master’s research under Dr. Kathleen Page, focusing on the role of prenatal dexamethasone treatment on serotonin receptor 5HT1A function. In 2010, he joined Dr. Stanley Perlman’s group at the University of Iowa for graduate research, studying the role of lipid mediators in modulating the immune response to coronaviruses, including SARS-CoV. After a brief postdoctoral stint at the NIH with Dr. Katrin Mayer-Barber, he returned to the University of Iowa to join Dr. Noah Butler’s lab. In the Butler Lab, he worked on elucidating the mechanisms contributing to suboptimal humoral immune response following Plasmodium infection. His postdoctoral work has revealed that the early plasmablast response during Plasmodium infection impairs the development and function of germinal center-derived B cell responses, with hemolysis and phosphatidylserine exposure identified as key factors contributing to plasmablast accumulation. Dr. Vijay joined the faculty of the Center for Cancer Cell Biology, Immunology, and Infection in July 2021.

Current Research Focus

A key feature of our immune system is its ability to remember previous infections and mount a rapid response to prevent reinfection. Vaccine efficacy relies heavily on the durability and quality of this immunological memory, primarily involving memory B cells (MBCs) generated through germinal center (GC) reactions in secondary lymphoid organs. However, immune memory against many pathogens remains insufficient, leading to recurrent infections. Malaria exemplifies this issue, with its inadequate immune memory causing severe consequences. Affecting half of the world’s population, malaria is one of the most widespread vector-borne diseases and caused over 600,000 deaths in 2020. The effective clearance of the Plasmodium parasite and sustained immunity rely on antibodies produced by GC-derived long-lived plasma cells (LLPCs) and MBCs, supported by CD4 T follicular helper (Tfh) cells. The Vijay Lab’s primary goal is to uncover the molecular and cellular immune mechanisms that lead to suboptimal immune memory in malaria and to develop host-directed immunomodulatory interventions to address this critical public health challenge.

Currently projects in the lab are:

1. To investigate the role of 4-1BB- 4-1BBL axis in governing humoral immune response following Plasmodium infection. This project is based on the following observations: (i) basal 4-1BB-4-1BBL signaling is required for protection from Plasmodium infection (ii) exogenous ligation of 4-1BB using an anti -4-1BB agonizing monoclonal antibody (3H3) in Plasmodium-infected mice delays effector humoral immune response but provides enhanced memory-mediated protection from repeat infections, (iii) 3H3 treatment induces robust expression of EOMES in CD4 T cells; conditional deletion of Eomes restores the effector response but reverses the observed enhanced protection (iv) use of 3H3 promotes the generation of a superior MBC pool and finally (v) adoptive transfer of MBCs from 3H3-treated-Plasmodium-infected mice confers enhanced protection. Our goal with this project is to address how a delayed acute humoral response (following exogenous ligation of 4-1BB) results in an enhanced MBC response and whether this therapeutic approach can be used to enhance protection following vaccination.
2. To investigate the role of TAM receptors in modulating humoral immune response against malaria. Our previous research into the causes of suboptimal humoral immune responses during malaria has led to several key findings, both published and unpublished: (i) Plasmodium infection is linked to hemolytic anemia and splenic hypoxia, (ii) hemolysis-associated phosphatidylserine (PtS) serves as a molecular signal driving the accumulation of effector (EF) short-lived plasmablasts (PBs), (iii) these EF short-lived PBs impair the anti-Plasmodium immune response by acting as a ‘nutrient sink,’ (iv) Axl-/- B cells show impaired differentiation into EF short-lived PBs, and (v) blocking PtS binding during Plasmodium infection reduces the accumulation of these immunosuppressive PBs and enhances the germinal center response. This project is aimed at exploring key molecular targets and signaling pathways driven by AXL that may modulate humoral immune response against parasitic infections. Successful completion of this project will have broader implications for other diseases where hemolytic anemia and associated plasmablast accumulation have been reported, including but not limited to COVID-19, Trypanosomiasis, and Dengue.

The lab is constantly in search of excellent graduate students.

Current Lab Members

Carolina Caloba, M.S., Graduate Student
carolina.caloba@my.rfums.org

Taylor Lyons, B.S., Research Technician
taylor.lyons@rosalindfranklin.edu

Lab Alumni

Kateryna Malkina, Summer Intern, Lake Forest College
Current position: Graduate student, UC Santa Barbara

Lijo John, DVM, Ph,D. Postdoctoral Fellow
Current position: Assistant Professor, KVASU, Kerala, India

Publications

1. John L, and Vijay R. (2024) Role of TAM receptors in antimalarial humoral immune response. Pathogens 2024, 13(4), 298;
2. Caloba C, Sturtz AJ, Ramachandran A, John L, Malkina K, Minns AM, Lindner SE, Vijay R. (2023) Exogenous 4-1BB co-stimulation enhances memory B cell response during malaria. bioRxiv. 2023 Sep12; https://doi.org/10.1101/2023.09.12.557411
3. Marques-da-Silva C, Peissig K, Walker MP, Shiau J, Kyle DE, Vijay R, Lindner SE, Kurup SP. Direct type I interferon signaling in hepatocytes control malaria. Cell Reports 2022. doi
4. Lefebvre MN, Surette FA, Anthony SM, Vijay R, Jensen IJ, Pewe LL, Hancox LS, Braeckel-Budimir NV, van de Wall S, Urban SL, Mix MR, Kurup SP, Badovinac VP, Butler NS, Harty JT. Expeditious recruitment of circulating memory CD8 T cells to the live facilitates control of malaria. Cell Reports 2021.Doi: 10.1016/j.celrep.2021.109956
5. Anthony SM, Braeckel-Budimir NV, Moioffer SJ, van de Wall S, Shan Q, Vijay R, Sompallae R, Hartwig SM, Jensen IJ, Varga SM, Butler NS, Xue HH, Badovinac VP and Harty JT. Protective function and durability of mouse lymph-node resident memory CD8+ T cells. eLife 2021. doi10.7554/eLife.68662
6. Rogers KJ, Vijay R and Butler NS. Anti-malarial humoral immunity: the long and short of it. Microbes and Infection, 2021 May. doi:10.1016/j.micinf.2021.104807
7. Vijay R^*, Guthmiller JJ^*, Sturtz AJ, Crooks S, Johnson JT, Li L, Lan LY, Pope RL, Chen Y, Rogers KJ, Dutta N, Toombs JE, Wilson ME, Wilson PC, Brekken RA and Butler NS. Hemolysis-associated phosphatidylserine exposure promotes polyclonal plasmablast differentiation. J Exp Med 2021 April. doi.org/10/1084/jem.2020359. ^* Co-lead authors
8. Vijay R^*, Guthmiller JJ^*, Sturtz AJ, Surette FA, Rogers KJ, Sompallae RR, Fengyin L, Pope RL, Chan J, Rivera FL, Andrew D, Webb L, Maury WJ, Xue HH, Engwerda CR, McCarthy JS, Boyle MJ, Butler NS. Plasmodium-induced early plasmablasts act as a nutrient sink that delays humoral immunity. Nat Immunol 2020 July. doi:10.1038/s41590-020-0678-5. ^* Co-lead authors
9. Surette FA, Guthmiller JJ, Vijay R, Strutz A, McClellan BL, Pack AD, Stock MR, Zander RA and Butler NS. Extra-follicular CD4 T cell-derived IL-10 functions rapidly and transiently to support anti-Plasmodium humoral immunity PLos Path 2021 February.doi:10.1371/e1009288.
10. Rogers K, Shtanko O, Vijay R, Mallinger L, Butler NS and Maury W. Acute Plasmodium infection promotes resistance to Ebola virus infection via type 1 immunity. Cell Reports. 2020 March. doi:10.1016/j/celrep.2020.02.104
11. Kurup SP, Anthony SM, Hancox LS, Vijay R, Pewe LL, Moioffer, S, Sompallae R, Janse CJ, Khan, SM and Harty JT. Dendritic cells acquire Plasmodium from hepatocytes to prime CD8 T cell immunity to liver-stage malaria. Cell Host Microbe. 2019 April 10;25(4):565-577.e6. doi: 10.1016/j.chom.2019.02.014. Epub 2019 Mar 21.
12. Hua X^*, Vijay R^*, Athmer J, Meyerholz D.K, Pagedar N, Tilley S and Perlman S. Nasal Priming by a murine coronavirus provides protective immunity against lethal heterogenous virus pneumonia. JCI Insight. 2018 Jun 7;3(11). pii: 99025. doi: 10.1172/jci.insight.99025. ^* Co-lead authors
13. Smith LK, Boukhaled GM, Condotta SA, Mazouz S, Guthmiller JJ, Vijay R, Butler NS, Bruneau J, Shoukey NH, Krawczyk, CM and Richer MJ. Interleukin-10 directly inhibits CD8⁺T cells function by enhancing N-glycan branching to decreases antigen sensitivity. Immunity. 2018 Feb 20;48(2):299-312.e5. doi: 10.1016/j.immuni.2018.01.006.
14. Zander RA, Vijay R, Pack AD, Guthmiller JJ, Graham AC, Lindner SE, Vaughan AM, Kappe SHI and Butler NS. Th1-like Plasmodium-specific memory CD4 T cells support humoral immunity. Cell Rep. 2017 Nov 14;21(7):1839-1852. doi: 10.1016/j.celrep.2017.10.077.
15. Rivera-Correa J, Guthmiller JJ, Vijay R, Fernandez-Arias C, Pardo-Ruge MA, Gonzalez S, Butler NS and Rodriguez A. Plasmodium DNA-mediated TLR9 activation of T-bet₊ B cells contributes to autoimmune anaemia during malaria. Nat Commun. 2017 Nov 3;8(1):1282. doi: 10.1038/s41467-017-01476-6.
16. Vijay R, Fehr AR, Janowski AM, Athmer J , Wheeler D, Grunewald, M, Kurup SP , Sompallae R , Sutterwala F S , Narumiya S and Perlman S. Prostaglandin D2/DP1 signaling suppresses virus-induced inflammasome activation. Proc Natl Acad Sci U S A. 2017 Jun 19. pii: 201704099. doi: 10.1073/pnas.1704099114.
17. Zhao J, Vijay R, Zhao J, Gale M Jr, Diamond MS and Perlman S. MAVS Expressed by Hematopoietic Cells Is Critical for Control of West Nile Virus Infection and Pathogenesis. J Virol. 2016 Jul 27;90(16):7098-108. doi: 10.1128/JVI.00707-16.
18. Perlman S and Vijay R. Middle East Respiratory Syndrome Vaccines. Int J Infect Dis. 2016 Jun;47:23-8. doi: 10.1016/j.ijid.2016.04.008.
19. Channappanavar R, Fehr A.R, Vijay R, Mack M and Perlman S. Dysregulated type I IFN and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV infected mice. Cell Host Microbe. 2016 Feb 10;19(2):181-93. doi: 10.1016/j.chom.2016.01.007.
20. Vijay R and Perlman S. Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome. 2015 Curr Opin Virol. 2016 Feb;16:70-6. doi: 10.1016/j.coviro.2016.01.011. Epub 2016 Feb 12.
21. Vijay R, Hua H,. Meyerholz D.K, Miki Y, Yamamoto K, Gelb M, Murakami M and Perlman S. 2015.Critical role of Phospholipase A₂ group IID in age-related susceptibility to Severe Acute Respiratory Syndrome-CoV infection. J Exp Med. 2015. doi: 10.1084/jem.20150632. Epub 2015 Sep 21.