Inefficient N2-like neutrophils are promoted by androgens during infection
Date
2018Author
Peinetti, Nahuel
Leimgruber, Carolina
Menezes, Gustavo B.
Maldonado, Cristina Alicia
Quintar, Amado Alfredo
Scalerandi, María Victoria
Cuello Rubio, Mariana Micaela
Nicola, Juan Pablo
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Neutrophils are major effectors of acute inflammation against infection and tissue damage, with ability to adapt their phenotype according to the microenvironment. Although sex hormones regulate adaptive immune cells, which explains sex differences in immunity and infection, little information is available about the effects of androgens on neutrophils. We therefore aimed to examine neutrophil recruitment and plasticity in androgen–dependent and –independent sites under androgen manipulation. By using a bacterial model of prostate inflammation, we showed that neutrophil recruitment
was higher in testosterone-treated rats, with neutrophil accumulation being positively correlated to serum levels of testosterone and associated to stronger inflammatory signs and tissue damage. Testosterone also promoted LPS-induced neutrophil recruitment to the prostate, peritoneum, and liver sinusoids, as revealed by histopathology, flow
cytometry, and intravital microscopy. Strikingly, neutrophils in presence of testosterone exhibited an impaired bactericidal ability and a reduced myeloperoxidase activity. This inefficient cellular profile was accompanied by high expression of the anti-inflammatory cytokines IL10 and TGFβ1, which is compatible with the “N2-like” neutrophil phenotype
previously reported in the tumor microenvironment. These data reveal an intriguing role for testosterone promoting inefficient, anti-inflammatory neutrophils that prolong bacterial inflammation, generating a pathogenic environment for several conditions. However, these immunomodulatory properties might be beneficially exploited in autoimmune and other non-bacterial diseases.