Human Monocytes - CD14, CD16 - Ziegler-Heitbrock

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IFNs Reset the Differential Capacity of Human Monocyte Subsets to Produce IL-12 in Response to Microbial Stimulation.

Abstract

Human primary monocytes are composed of a minor, more mature CD16+(CD14low/neg) population and a major CD16neg(CD14+) subset. The specific functions of CD16+ versus CD16neg monocytes in steady state or inflammation remain poorly understood. In previous work, we found that IL-12 is selectively produced by the CD16+ subset in response to the protozoan pathogen, Toxoplasma gondii In this study, we demonstrated that this differential responsiveness correlates with the presence of an IFN-induced transcriptional signature in CD16+ monocytes already at baseline. Consistent with this observation, we found that in vitro IFN-gamma priming overcomes the defect in the IL-12 response of the CD16neg subset. In contrast, pretreatment with IFN-gamma had only a minor effect on IL-12p40 secretion by the CD16+ population. Moreover, inhibition of the mTOR pathway also selectively increased the IL-12 response in CD16neg but not in CD16+ monocytes. We further demonstrate that in contrast to IFN-gamma, IFN-alpha fails to promote IL-12 production by the CD16neg subset and blocks the effect of IFN-gamma priming. Based on these observations, we propose that the acquisition of IL-12 responsiveness by peripheral blood monocyte subsets depends on extrinsic signals experienced during their developmental progression in vivo. This process can be overridden during inflammation by the opposing regulatory effects of type I and II IFN as well as the mTOR inhibition.

Authors: Muglia Amancio A, Mittereder L, Carletti A, Tosh KW, Green D, Antonelli LR, Gazzinelli RT, Sher A, Jankovic D,
Journal: J Immunol;2021 Apr 1;206(7):1642-1652 doi:10.4049/jimmunol.2001194
Year: 2021
PubMed: PMID: 33627376 (Go to PubMed)