Event Abstract Back to Event Human macrophage polarization enhances opsonophagocytosis and inflammatory response of the stealth pathogen, Treponema pallidum Kelly L. Hawley1*, Adriana R. Cruz2, Jorge Cervantes1, 3, Carson Karanian4, Morgan LeDoyt4, Rodolfo Trujillo1, Lady G. Ramirez2, Justin Radolf1, 4, 5 and Juan C. Salazar1, 3, 4 1 University of Connecticut Health Center, Department of Pediatrics, United States 2 Centro Internacional de Entrenamiento e Investigaciones Médicas CIDEIM, Colombia 3 Connecticut Children’s Medical Center, Division of Infectious Disease and Immunology, United States 4 University of Connecticut Health Center, Departments of Medicine, United States 5 University of Connecticut Health Center, Genetics and Developmental Biology, United States Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochete Treponema pallidum (Tp). Congenital syphilis, a result of transplacental migration of Tp, is a major global threat to child health. Clinical manifestations result from the treponeme's ability to elicit a robust immune response while evading host defenses; this duality is best exemplified during the florid, disseminated stage called secondary syphilis (SS). SS lesions contain copious spirochetes along with a mixed cellular infiltrate consisting of CD4 T cells, CD8 T cells, NK cells, plasma cells and macrophages (MΦ). In the rabbit model, Tp are cleared by MΦs via antibody (Ab)-mediated opsonophagocytosis. Previously, we demonstrated that human syphilitic serum (HSS) promotes efficient uptake of Tp by human monocytes and that opsonophagocytosis of Tp markedly enhances cytokine production. The purpose of this study is to establish a potential role for MΦs and opsonic Ab in clearance of treponemes and generation of tissue-based inflammation during human syphilis. We used monocyte-derived MΦs to develop an ex vivo model for studying spirochete-MΦ interactions and cellular responses (e.g., phagosomal signaling) following uptake of Tp. We also examined SS skin biopsies for evidence of internalization of Tp by dermal MΦs. In the presence or absence of HSS, untreated (i.e., no M-CSF or IFNγ) MΦs internalized low numbers of Tp and secreted little cytokine (e.g., TNF and IL-6). In contrast, untreated MΦs internalized unopsonized Lyme disease spirochetes (Borrelia burgdorferi) and secreted robust levels of cytokines. Maturation of MΦs with M-CSF and IFNγ [MΦ(IFNγ)] resulted in increased TLR signaling and enhanced expression of the Fc receptors CD64 and CD16. Importantly, IFNγ polarization of MΦs led to a statistically significant, but modest, increase in opsonophagocytosis of Tp and cytokine production. Interestingly, immunofluorescence analysis of SS skin biopsies yielded only scant evidence for internalization of Tp by dermal MΦs. Our ex vivo studies demonstrate a potential role for MΦs in clearance of Tp during human syphilis. On the other hand, the in vivo data suggest that Tp, the stealth pathogen, is adept at evading MΦ-dependent clearance and suggest the possibility of MΦ-independent clearance mechanisms. Acknowledgements We gratefully acknowledge the patients who participated in this study. This work received support from NIAID grant A1090166, CCMC Arrison and Burr Curtis Research Funds and Fogarty/NIH R03TW009172. Keywords: Macrophages, Syphilis, FcγR, phagosomal signaling, Clearance Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Oral Presentation Topic: Innate Immunity Citation: Hawley KL, Cruz AR, Cervantes J, Karanian C, LeDoyt M, Trujillo R, Ramirez LG, Radolf J and Salazar JC (2015). Human macrophage polarization enhances opsonophagocytosis and inflammatory response of the stealth pathogen, Treponema pallidum. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00306 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 May 2015; Published Online: 15 Sep 2015. * Correspondence: PhD. Kelly L Hawley, University of Connecticut Health Center, Department of Pediatrics, Farmington, Connecticut, United States, Hawley@uchc.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kelly L Hawley Adriana R Cruz Jorge Cervantes Carson Karanian Morgan LeDoyt Rodolfo Trujillo Lady G Ramirez Justin Radolf Juan C Salazar Google Kelly L Hawley Adriana R Cruz Jorge Cervantes Carson Karanian Morgan LeDoyt Rodolfo Trujillo Lady G Ramirez Justin Radolf Juan C Salazar Google Scholar Kelly L Hawley Adriana R Cruz Jorge Cervantes Carson Karanian Morgan LeDoyt Rodolfo Trujillo Lady G Ramirez Justin Radolf Juan C Salazar PubMed Kelly L Hawley Adriana R Cruz Jorge Cervantes Carson Karanian Morgan LeDoyt Rodolfo Trujillo Lady G Ramirez Justin Radolf Juan C Salazar Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.