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

Rabindra K. Mandal,Ruth Namazzi,Dibyadyuti Datta,Joshua E. Denny,Chandy C. John,Nathan W. Schmidt,Robert O. Opoka

doi:10.1016/j.celrep.2021.109094

Rabindra K. Mandal, Ruth Namazzi + Show 5 more

Open Access

https://doi.org/10.1016/j.celrep.2021.109094

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Abstract

Gut microbiota educate the local and distal immune system in early life to imprint long-term immunological outcomes while maintaining the capacity to dynamically modulate the local mucosal immune system throughout life. It is unknown whether gut microbiota provide signals that dynamically regulate distal immune responses following an extra-gastrointestinal infection. We show here that gut bacteria composition correlated with the severity of malaria in children. Using the murine model of malaria, we demonstrate that parasite burden and spleen germinal center reactions are malleable to dynamic cues provided by gut bacteria. Whereas antibiotic-induced changes in gut bacteria have been associated with immunopathology or impairment of immunity, the data demonstrate that antibiotic-induced changes in gut bacteria can enhance immunity to Plasmodium. This effect is not universal but depends on baseline gut bacteria composition. These data demonstrate the dynamic communications that exist among gut bacteria, the gut-distal immune system, and control of Plasmodium infection.

Highlights

Gut microbiota, the community of microorganisms living in the gastrointestinal tract, have diverse effects on host biology
We show in mice that gut bacteria provide cues that dynamically modulate parasite burden and spleen germinal center (GC) reactions, providing a potential explanation for the protection from severe malaria associated with stool bacteria compositions in the Ugandan children
Stool bacteria populations correlate with severity of malaria in Ugandan children To determine whether gut bacteria composition is associated with severity of malaria in humans, bacteria populations were analyzed by Multiple 16S Variable Region Species-Level Identification (MVRSION) (Schriefer et al, 2018) in stool collected from Ugandan children who had severe malaria anemia (SMA; n = 40) or community control children who were otherwise healthy but had asymptomatic Plasmodium falciparum (Pf) infections (Pf Pos; n = 7) or were Pf negative (Pf Neg; n = 28) (Figure 1A)

Summary

Introduction

The community of microorganisms living in the gastrointestinal tract, have diverse effects on host biology. The reported increase in serum IgE after weaning is consistent with gut microbiota composition in mice programming the immune system during weaning through induction of regulatory T cells to resist inflammatory pathologies into adulthood (Al Nabhani et al, 2019). Events in early life that can alter gut microbiota composition (e.g., caesarean section, formula feeding, infection/inflammation, and antibiotic exposure) can pathologically imprint the immune system and increase the risk of childhood asthma and atopy (Arrieta et al, 2015; Fujimura et al, 2016; Shao et al, 2019). It has been shown that humans treated with antibiotics before administration of the seasonal influenza vaccine exhibited reduced

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