Abstract
Liver macrophages internalize circulating bloodborne parasites. It remains poorly understood how this process affects the fate of the macrophages and T cell responses in the liver. Here, we report that infection by Trypanosoma brucei induced depletion of macrophages in the liver, leading to the repopulation of CXCL16-secreting intrahepatic macrophages, associated with substantial accumulation of CXCR6+CD4+ T cells in the liver. Interestingly, disruption of CXCR6 signaling did not affect control of the parasitemia, but significantly enhanced the survival of infected mice, associated with reduced inflammation and liver injury. Infected CXCR6 deficient mice displayed a reduced accumulation of CD4+ T cells in the liver; adoptive transfer experiments suggested that the reduction of CD4+ T cells in the liver was attributed to a cell intrinsic property of CXCR6 deficient CD4+ T cells. Importantly, infected CXCR6 deficient mice receiving wild-type CD4+ T cells survived significantly shorter than those receiving CXCR6 deficient CD4+ T cells, demonstrating that CXCR6+CD4+ T cells promote the mortality. We conclude that infection of T. brucei leads to depletion and repopulation of liver macrophages, associated with a substantial influx of CXCR6+CD4+ T cells that mediates mortality.
Highlights
The liver is the biggest internal organ with important functions of both metabolism and immunity [1]
We have previously shown that liver macrophages engulf African trypanosomes through complement receptor CRIg
We show that liver macrophages were depleted during infection of trypanosome parasites T. brucei and repopulated
Summary
The liver is the biggest internal organ with important functions of both metabolism and immunity [1]. KCs are liver-resident macrophages that adhere to the endothelial cells of the liver sinusoids [1]. Like tissue resident macrophages in other organs, KCs are embryonic origin and self-renewing under steady condition [7,8,9]. KCs infected by bacterial pathogen Listeria monocytogenes undergo rapid necroptotic death, followed by replenishment of the depleted KCs with circulating monocytes and subsequent tissue repair [12]. It remains poorly understood how this process affect adaptive immunes responses, T cell responses in the liver following phagocytosis of bloodborne parasites by KCs
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