Down-modulation of effector functions in NK cells upon T. gondii infection.

5 years ago

Down-modulation of effector functions in NK cells upon T. gondii infection.

Lambert H, Fuks JM, Barragan A, Kadri N, Du A, Chambers BJ, Campbell TM, Mansfield IO, James J, Liu L, Kanatani S, De Koning T, Angbjär CM, Weidner JM, Carow B, Sultana AM

The obligate intracellular parasite Toxoplasma gondii (T. gondii) can actively infect any nucleated cell type including cells from the immune system. Rapid transfer of T. gondii from infected dendritic cells to effector natural killer (NK) cells may contribute to the parasite's sequestration and shielding from immune recognition shortly after infection. However, subversion of NK cell functions, such as cytotoxicity or production of pro-inflammatory cytokines such as IFNγ, upon parasite infection might also be beneficial to the parasite. In the present study, we have investigated the effects of T. gondii infection on NK cells. In vitro, infected NK cells were found to be poor at killing target cells, and had reduced IFNγ production. This could be attributed in part to the inability of infected cells to form conjugates with their target cells. However even upon NK1.1 crosslinking of NK cells, the infected NK cells also exhibited poor degranulation and IFNγ production respectively. Similarly NK cells infected in vivo were also poor at killing target cells and producing IFNγ. Increased TGFβ production was observed in infected NK cells as well as increased expression of SHP-1 in the cytosol of infected NK cells upon infection. However phosphorylation of STAT4 was not altered in infected NK cells suggesting that transcriptional regulation mediates the reduced IFNγ production, which was confirmed by qPCR. These data suggest that infection of NK cells by T. gondii impairs their target cell recognition and cytokine release, two mechanisms that independently could enhance T. gondii survival.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28760930

DOI: PubMed:28760930