Abstract
It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.
Highlights
Leptospirosis is a worldwide infectious disease caused by Leptospira species, with a recent estimate of 1 million cases per year [1]
We analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15
TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls
Summary
Leptospirosis is a worldwide infectious disease caused by Leptospira species, with a recent estimate of 1 million cases per year [1]. During the first two weeks of leptospirosis, PMN count is usually characterized by a moderate increase and is correlated to disease severity [4,5,6]. This is a non-specific feature of acute sepsis and bacteremia in general. Recent findings suggest that the production of neutrophil’s extracellular traps (NETosis) could be a reliable mechanism of defense to prevent bacterial dissemination [11] Beside these weapons, pathogenic leptospires are able to evade the immune response of PMN. A clearer understanding of the role of PMN during leptospirosis warrants further studies
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