Dynamic modulation of spleen germinal center reactions by gut bacteria during systemic infection

Gut microbiota educate the immune system in early life to imprint long-term immunological outcomes while also maintaining the capacity to dynamically modulate the local mucosal immune system throughout life. It is unknown if gut microbiota provide signals that dynamically regulate systemic immune responses following an extra-gastrointestinal infection. We show here that gut bacteria provide cues that dynamically modulate germinal center reactions and progression of Plasmodium infection in mice. Gut bacteria composition was also shown to correlate with the severity of malaria in humans. Whereas antibiotic-induced changes in gut bacteria has often been associated with immunopathology or impairment of host immunity, our data demonstrate that antibiotic-induced changes in gut bacteria populations can enhance humoral immunity to Plasmodium. This effect is not universal, but instead depends on the baseline gut bacteria composition. These data provide new insight into the dynamic communications that exist between gut bacteria and the systemic immune response as well as the plasticity of an ongoing humoral immune response.