A Subset of Neutrophils Expressing Markers of Antigen-Presenting Cells in Human Visceral Leishmaniasis

Background. Visceral leishmaniasis (VL) is a potentially fatal parasitic disease associated with fever, cachexia and impaired protective T-cell responses against the parasite. Methods. Peripheral blood leukocytes from 105 subjects with VL and healthy control subjects from the endemic region of Muzaffarpur, Bihar, India, were compared using flow cytometry and reverse-transcriptase quantitative polymerase chain reaction. Findings were correlated with clinical data. Results. An expanded population of low-density neutrophils that expressed HLA-DR, CD80 and CD86 was observed in subjects with VL. This neutrophil population contracted after successful treatment of disease. Plasma from patients with acute VL was able to induce similar high-level HLA-DR expression in neutrophils from healthy subjects. HLA-DR+ neutrophils from subjects with VL did not stimulate T-cell proliferation, but they did express higher programmed cell death ligand-1 (PDL1) than other neutrophils, and lymphocytes of the same subjects expressed high programmed cell death 1 (PD1). Conclusions. Patients with acute VL have expanded circulating low-density neutrophils expressing markers of antigen presentation, which diminish after treatment. Development of HLA-DR+ neutrophils is stimulated, at least in part, by components of plasma from patients with acute disease. Although we found no evidence that they act as antigen-presenting cells, these neutrophils expressed markers implicating a role in T-cell exhaustion.