Large Peritoneal Macrophages influence CD8+ T cell activation and parasite control during acute Trypanosoma cruzi infection

Abstract Resident peritoneal macrophages consist of two subpopulations with distinct origin, sizes and phenotype named Large Peritoneal Macrophages (LPMs) and Small Peritoneal Macrophages (SPMs). While LPMs are long-live cells that origin in embryonic yolk sac and can self-replenish after mild loss, SPMs are short-live cells that derive from blood monocytes and are in continuous replenishment. Under homeostasis, LPMs constitute more than 70% of total CD11b+ cells, but during infection or inflammation drastically dampen. As LPMs have been reported to be essential for CD8+ T cell priming and replication control in parasite infections, we aimed to study their role in the context of Chagas’ disease. We observed a reduction in LPMs during acute phase of T. cruzi infection in BALB/c mice that did not restore in chronic phase. Instead, this subset was replaced by a population with intermediate expression of F4/80, previously described as ‘inflammatory macrophages’, but with a mixed phenotype activation in this case. Besides, this F4/80int population could also be associated with truncated maturation of monocytes to resident macrophages. In this work, LPMs showed higher CD80+ and lower PD-L1+ cells frequencies and produced more IL-12 and TNF than SPMs. This profile may favor CD8+ T-cell activation, reflected by increased CD69 expression and Perforin/Granzyme B production. Replenishment of LPMs by adoptive transfer of PEMs was associated with reduced parasitemia and enhanced splenic CD8+ T-cell activation. Thus, LPMs may contribute to CD8+ T-cell responses and parasite control during acute T. cruzi infection.