title: Vibrio cholerae porin OmpU mediates M1-polarization of macrophages/monocytes via TLR1/TLR2 activation.
abstract: 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 NFκB p65 subunit. We also observed that blocking of the TLR1, TLR2, IRAK1, and NFκB affected OmpU-mediated production of M1-associated pro-inflammatory cytokines such as TNFα and IL-6.
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, Mohali, Punjab 140306, India.
authors.forename: Junaid
authors.initials: J
authors.lastname: Khan
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, Mohali, Punjab 140306, India.
authors.forename: Praveen K
authors.initials: PK
authors.lastname: Sharma
authors.affiliation: Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector 81, SAS Nagar, Mohali, Punjab 140306, India. Electronic address: arunika@iisermohali.ac.in.
authors.forename: Arunika
authors.initials: A
authors.lastname: Mukhopadhaya
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D055503:Protein Multimerization; D034622:RNA Interference; D015398:Signal Transduction; D051194:Toll-Like Receptor 1 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014734:Vibrio cholerae / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D015850:Interleukin-6; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C096349:OmpU protein, Vibrio cholerae; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D053592:Interleukin-1 Receptor-Associated Kinases
keywords: M1/M2 polarization; OmpU; Porin; Toll-like receptor