Research Interest: Immune Response to Plasmodium
Ph.D., Drexel University College of Medicine, Philadelphia, PA
Postdoctoral Training: University of Pennsylvania, School of Veterinary Medicine, Philadelphia, PA
The protozoan parasite Plasmodium is the causative agent of malaria, which remains one of the most prominent public health challenges in the world today. Malaria results in the death of more children worldwide than any other infectious disease. The development of a malaria vaccine is a high-priority goal, but in order to design and evaluate vaccine candidates, a further understanding of how protective immunity is generated in terms of induction, effector mechanisms, and memory will be needed. Currently, there is conflicting evidence as to whether long-term memory responses against Plasmodium can be maintained, which could pose a problem for the development of an effective vaccine for humans.
The generation of Plasmodium species adapted to infect inbred strains of mice has been instrumental for assessing parasite-specific immune responses in vivo and has illustrated that protective immunity to blood-stage infection with Plasmodium requires a parasite-specific CD4+ T-cell response as well as high-titer neutralizing antibodies (Abs) to effectively control parasite replication. The laboratory primarily focuses on experimental murine infections with Plasmodium yoelii 17X and P. chabaudi AS, two non-lethal self-resolving rodent species of Plasmodium. These two species provide well-characterized models for understanding the events that lead to the production and maintenance of a protective Ab response against this parasite. During Plasmodium infection, the spleen serves as the primary site for removal of parasitized red blood cells, generation of immunity and production of new red blood cells. The laboratory is interested in the events that lead to the formation, regulation and maintenance of germinal centers, which serve as the site of antigen-specific B cell proliferation, and immunoglobulin isotype switching and somatic hypermutation within the spleen. In particular, we are interested in defining the factors that are involved in the formation and maintenance of memory B cells and plasma cells after primary and secondary infection. Additionally, we are interested understanding how stromal cell populations in the spleen regulate the humoral response.
Wikenheiser DJ, Brown SL, Lee J, Stumhofer JS. NK1.1 expression defines a population of CD4+ effector T cells displaying Th1 and Tfh cell properties that support early antibody production during Plasmodium yoelii infection. Front Immunol. Oct 15;9:2277. PMCID: PMC6190288.
Ghosh D, Brown SL, Stumhofer JS. IL-17 promotes differentiation of splenic LSK– lymphoid progenitors into B cells following Plasmodium yoelii infection. J Immunol. 2017 Sep 1;199(5):1783-1795. Epub 2017 Jul 21. PMCID: PMC5585076.
Ghosh D, Wikenheiser DJ, Kennedy B, McGovern KE, Stuart JD, Stumhofer JS. An atypical splenic B cell progenitor supports antibody production during Plasmodium infection in mice. J. Immunol. 2016 Sept 1;197(5):1788-800. Epub 2016 Jul 22. PMCID: PMC4992648.
Wikenheiser DW, Stumhofer JS. ICOS co-stimulation during infection: friend or foe? Frontiers in Immunol. 2016 Aug 10;7:304. PMCID: PMC4979228.
Wikenheiser DJ, Ghosh D, Kennedy B, Stumhofer JS. The costimulatory molecule ICOS regulates host TH1 and follicular Th cell differentiation in response to Plasmodium chabaudi chabaudi AS infection. J. Immunol. 2016 Jan 15;196(2):778-91. Epub 2015 Dec 14. PMCID: PMC4705592.
Menyaev YA, Carey KA, Nedosekin DA, Sarimollaoglu M, Galanzha EI, Stumhofer JS, Zharov VP. Preclinical photoacoustic model: application for ultrasensitive single cell malaria diagnosis in large vein and artery. Biomedical Optics Express 2016 Aug 24;7(9):3643-3658. PMCID: PMC5030038.
Cai C, Carey KA, Nedosekin DA, Menyaev YA, Sarimollaoglu M, Galanzha EI, Stumhofer JS, Zharov VP. In vivo photoacoustic flow cytometry for early malaria diagnosis. Cytometry A. 2016 Jun;89(6):531-42.
Stumhofer JS, Loke P. Parasites: What are They Good for? Current Immunol. Rev. 2013 August 1; 9(3): 120-128. PMCID: PMC3969036.
Ghosh D, Stumhofer JS. Do You See What I See: Recognition of Protozoan Parasites by Toll-Like Receptors. Current Immunol. Rev. 2013, August 1; 9(3): 129-140. PMCID: PMC4223800.
Stumhofer, JS, Silver JS, Hunter CA. IL-21 is required for optimal antibody production and T-cell responses during chronic Toxoplasma gondii infection. PLOS ONE. 2013 May 7;8(5):e62889. PMCID: PMC3647013.
Hall AO, Beiting DP, Tato C, John B, Oldenhove G, Lombana CG, Pritchard GH, Silver JS, Bouladoux N, Stumhofer JS, Harris TH, Grainger J, Wojno ED, Wagage S, Roos DS, Scott P, Turka LA, Cherry S, Reiner SL, Cua D, Belkaid Y, Elloso MM, Hunter CA. The cytokine interleukin 27 and interferon-γ promote distinct Treg cell populations required to limit infection-induced pathology. Immunity. 2012 Sep 21;37(3):511-23. Epub 2012 Sep 13. PMCID: PMC3477519.
Villegas-Mendez A, Greig R, Shaw TN, de Souza JB, Gwyer Findlay E, Stumhofer JS, Hafalla JC, Blount DG, Hunter CA, Riley EM, Couper KN. IFN-γ-producing CD4+ T cells promote experimental cerebral malaria by modulating CD8+ T cell accumulation within the brain. J. Immunol. 2012 Jul 15;189(2):968-79. Epub 2012 Jun 20. PMCID: PMC3393641.
Dr. Stumhofer’s publications on PubMed.