Minelva R. Nanton

     Email: nanto001@umn.edu

     Year Entered: 2008

     Degrees Received:
     State University of New York at Binghamton
     Biochemistry major
     B.S., 2006

     Honors and Awards:
-Ruth L. Kirschstein National Research Service Award for Predoctoral
     MD/PhD Fellows, National Institute of Allergy and Infectious Disease,
     -Phillips Neighborhood Clinic Operations Chair, 2010-11
     -John H. Wallace Fellowship, Autumn Immunology Conference,
     Chicago, IL, 2010
     -Honors in Medical Microbiology and Medical Genetics, UMN Medical
     School, 2009
-The Melvin Denis Memorial Travel Award, MD/PhD Student Conference, Keystone, Colorado 2008
-Diversity of Views and Experiences (DOVE) Fellowship, University of Minnesota Graduate School, 2006-2007

Thesis Advisor: Stephen J. McSorley, Ph.D., co-advisor: SingSing Way, M.D./Ph.D.

Thesis Research: Characterization of B cell Responses to Salmonella Infection

Typhoid fever and disseminated non-typhoidal bacteremia remain critical human health issues, with much of the disease burden falling on infants and children in sub-Saharan Africa. Although B cells are required for adaptive immunity to Salmonella infection the main mechanisms of protection are unclear. To determine whether the B cell mediated protective immunity is antibody dependent; we immunized wildtype, B cell deficient, antibody deficient and class-switched antibody deficient mice with attenuated Salmonella and examined resistance to secondary infection. While B cell deficient mice succumbed to secondary infection, mice with intact B cells lacking all antibodies or class-switched antibodies showed little deficiency in acquired immunity to virulent Salmonella. These changes in susceptibility of B cell deficient mice to virulent Salmonella challenge correlated with significant impairment of CD4 T cell IFNγ production post secondary challenge. To extend these observations into understanding the endogenous B cell response to Salmonella, we employed the use of a novel B cell tetramer reagent. We show that Salmonella-specific B cell proliferation, activation, germinal center formation and antibody production are robust but largely restricted to time points after Salmonella has been cleared. This delay in the kinetics of B cell responses to Salmonella explains their necessity in clearing a secondary, but not primary infection. Together, our data suggest that B cells are indispensible for acquired immunity to virulent Salmonella via an antibody-independent mechanism and are essential for developing protective T cell immunity.

Publications (pubmed):

Ertelt JM, Johanns TM, Mysz MA, Nanton MR, Rowe JH, Aguilera MN, Way SS. Selective culling of high avidity antigen-specific CD4(+) T cells after virulent Salmonella infection. Immunology. 2011 Dec;134(4):487-97. doi: 10.1111/j.1365-2567.2011.03510.x.

Jackson A, Nanton MR, O’Donnell H, Akue AD, and McSorley SJ. Innate Immune Activation during Salmonella Infection Initiates Extramedullary Erythropoiesis and Splenomegaly. J Immunol. 2010;185(10): 6198-6204.

Srinivasan A, Nanton M, Griffin A, McSorley SJ. Culling of activated CD4 T cells during typhoid is driven by Salmonella virulence genes. J Immunol. 2009;182:7838-7845.