期刊
IMMUNOBIOLOGY
卷 220, 期 11, 页码 1199-1209出版社
ELSEVIER GMBH, URBAN & FISCHER VERLAG
DOI: 10.1016/j.imbio.2015.06.009
关键词
M1/M2 polarization; Toll-like receptor; OmpU; Porin
类别
资金
- Department of Biotechnology (DBT), India (DBT) [BT/PR1205/MED/29/318/2011]
- IISER Mohali
Polarization of the monocytes and macrophages toward the M1 and M2 states is important for hosts' defense against the pathogens. Moreover, it plays a crucial role to resolve the overwhelming inflammatory responses that can be harmful to the host. Polarization of macrophages/monocytes can be induced by pathogen-associated molecular patterns (PAMPs). PAMP-mediated monocyte/macrophage polarization is important during the infection, as pathogen can suppress host immune system by altering the polarization status of the macrophages/monocytes. OmpU, an outer membrane porin protein of Vibrio cholerae, possesses the ability to induce pro-inflammatory responses in monocytes/macrophages. It is also able to down-regulate the LPS-mediated activation of the monocytes/macrophages. Such observation leads us to believe that OmpU may induce a state that can be called as M1/M2-intermediate state. In the present study, we evaluated a set of M1 and M2 markers in RAW 264.7 murine macrophage cell line, and THP-1 human monocytic cell line, in response to the purified OmpU protein. We observed that OmpU, as a PAMP, induced M1-polarization by activating the Toll-like receptor (TLR) signaling pathway. OmpU induced formation of TLR1/TLR2-heterodimers. OmpU-mediated TLR-activation led to the MyD88 recruitment to the TLR1/TLR2 complex. MyD88, in turn, recruited IRAK1. Ultimately, OmpU-mediated signaling led to the activation and subsequent nuclear translocation of the NF kappa B p65 subunit. We also observed that blocking of the TLR1,TLR2, IRAK1, and NF kappa B affected OmpU-mediated production of M1-associated pro-inflammatory cytokines such as TNB alpha and IL-6. (C) 2015 Elsevier GmbH. All rights reserved.
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