Learning from the research on amebiasis and gut microbiome: Is stimulation by gut flora essential for effective neutrophil mediated protection from external pathogens?

Abstract

Amebiasis, caused by intestinal infection with Entamoeba histolytica, is one of the leading causes of parasite infection-related mortality and morbidity globally. Although its pathogenesis, including determinant factors of infection outcome, remains unclear, recent clinical data indicate that the gut microbiome plays a role in determining the severity of amebiasis. Recently, we investigated the effects of the gut microbiome on neutrophil mediated protection from E. histolytica infection using a mouse model. We identified that surface expression of CXCR2 on neutrophils was diminished in mice with dysbiosis, which resulted in decreased neutrophil recruitment to the infection site, allowing more aggressive intestinal tissue damage by E. histolytica. Our results indicated that oxidase activity during E. histolytica infection was also diminished after dysbiosis, consistent with the results from prior research. Thus, the gut microbiome plays an important role in regulating neutrophil phenotype when fighting against external pathogens.

Keywords: CXCR2; amebiasis; chemokine receptor; gut microbiomes; neutrophils.

Figure 1.

Protection from E. histolytica invasion by neutrophils activated by gut microbes at the early phase (A) and exacerbation of tissue damage by neutrophils excessively activated by E. histolytica secreted proteins at the later phase (B) of infection. (A) Neutrophils are continuously stimulated by host gut microbes in the resting state before infection (①). These neutrophils are potent in protecting host intestinal epithelial cells from E. histolytica invasion (②). (B) However, once E. histolytica invades the submucosa, neutrophils excessively activated by E. histolytica secreted proteins and host proinflammatory cytokines (①’) exacerbate tissue damage (②’).