Gut Microbiota Composition Modulates the Magnitude and Quality of Germinal Centers during Plasmodium Infections
Morgan L. Waide,
Rafael Polidoro,
Whitney L. Powell,
Joshua E. Denny,
Justin Kos,
David A. Tieri,
Corey T. Watson,
Nathan W. Schmidt
Affiliations
Morgan L. Waide
Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
Rafael Polidoro
Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA
Whitney L. Powell
Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA
Joshua E. Denny
Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA
Justin Kos
Department of Biochemistry, University of Louisville, Louisville, KY, USA
David A. Tieri
Department of Biochemistry, University of Louisville, Louisville, KY, USA
Corey T. Watson
Department of Biochemistry, University of Louisville, Louisville, KY, USA
Nathan W. Schmidt
Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA; Ryan White Center for Pediatric Infectious Diseases and Global Health, Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, USA; Corresponding author
Summary: Gut microbiota composition is associated with human and rodent Plasmodium infections, yet the mechanism by which gut microbiota affects the severity of malaria remains unknown. Humoral immunity is critical in mediating the clearance of Plasmodium blood stage infections, prompting the hypothesis that mice with gut microbiota-dependent decreases in parasite burden exhibit better germinal center (GC) responses. In support of this hypothesis, mice with a low parasite burden exhibit increases in GC B cell numbers and parasite-specific antibody titers, as well as better maintenance of GC structures and a more targeted, qualitatively different antibody response. This enhanced humoral immunity affects memory, as mice with a low parasite burden exhibit robust protection against challenge with a heterologous, lethal Plasmodium species. These results demonstrate that gut microbiota composition influences the biology of spleen GCs as well as the titer and repertoire of parasite-specific antibodies, identifying potential approaches to develop optimal treatments for malaria.
