IRAK1 and IRAK4 signaling proteins are dispensable in the response of human neutrophils to Mycobacterium tuberculosis infection.

Abstract

The involvement of neutrophils in the host response to Mycobacterium tuberculosis (Mtb) infection is not as well recognized as the involvement of macrophages and dendritic cells. Thus, this study gives more insight on the impact of the virulent Mtb H37Rv strain on proapoptotic and proinflammatory functions of human neutrophils in vitro. We found that neutrophils are not able to kill Mtb during the infection process, probably due to the lack of reactive oxygen species and nitric oxide production in response to bacteria. However, infected neutrophils effectively released cytokines, chemoattractant interleukin (IL) 8 and proinflammatory IL-1β. Moreover, Mtb enhanced the early apoptosis of neutrophils at 2 h postinfection. Additionally, this proapoptotic and proinflammatory response of neutrophils to Mtb infection occurred in an IRAK1- and IRAK4-independent manner. We also found that Mtb did not affect the surface expression of Toll-like receptor (TLR) 2 and slightly enhanced the surface expression of TLR4, but did not influence mRNA levels of both TLRs during the infection process. In conclusion, we show that the inhibition of signaling proteins activated by MyD88-dependent pathway did not participate in the biological activity of neutrophils against Mtb.