Abstract
In HIV-infected individuals, a paradoxical clinical deterioration may occur in preexisting leprosy when highly active antiretroviral therapy (HAART)-associated reversal reaction (RR) develops. Leprosy–HIV co-infected patients during HAART may present a more severe form of the disease (RR/HIV), but the immune mechanisms related to the pathogenesis of leprosy–HIV co-infection remain unknown. Although the adaptive immune responses have been extensively studied in leprosy–HIV co-infected individuals, recent studies have described that innate immune cells may drive the overall immune responses to mycobacterial antigens. Monocytes are critical to the innate immune system and play an important role in several inflammatory conditions associated with chronic infections. In leprosy, different tissue macrophage phenotypes have been associated with the different clinical forms of the disease, but it is not clear how HIV infection modulates the phenotype of innate immune cells (monocytes or macrophages) during leprosy. In the present study, we investigated the phenotype of monocytes and macrophages in leprosy–HIV co-infected individuals, with or without RR. We did not observe differences between the monocyte profiles in the studied groups; however, analysis of gene expression within the skin lesion cells revealed that the RR/HIV group presents a higher expression of macrophage scavenger receptor 1 (MRS1), CD209 molecule (CD209), vascular endothelial growth factor (VEGF), arginase 2 (ARG2), and peroxisome proliferator-activated receptor gamma (PPARG) when compared with the RR group. Our data suggest that different phenotypes of tissue macrophages found in the skin from RR and RR/HIV patients could differentially contribute to the progression of leprosy.
Highlights
Macrophages play a central role in the pathogenesis of leprosy, a chronic infectious disease caused by the intracellular pathogen Mycobacterium leprae
Considering that HIV patients are more susceptible to the development of reversal reaction (RR), and monocytes and macrophages regulate the immune response and participate in the development of these reactions, being two important reservoirs for the HIV virus, the present study aimed to evaluate the profile of monocytes and macrophages in leprosy–HIV co-infected patients, with particular attention to innate immune markers associated with RR in co-infected patients
In order to investigate the cell phenotypes present in lesions from leprosy– HIV co-infected patients, with or without RR, we evaluated pro, and anti-inflammatory macrophage markers as well as markers that could be present in both macrophage phenotypes, depending on the environment (IDO, HMOX1, CD209)
Summary
Macrophages play a central role in the pathogenesis of leprosy, a chronic infectious disease caused by the intracellular pathogen Mycobacterium leprae. Previous studies demonstrated that skin macrophages from paucibacillary individuals present reduced phagocytic properties and higher. Frontiers in Immunology | www.frontiersin.org da Silva et al. Macrophage Polarization in Leprosy-HIV Patients antimicrobial activity, mediated by an interleukin (IL)-15dependent vitamin D activation and autophagy induction, presenting characteristics of classical activated macrophages [3, 4]. Skin cells from multibacillary patients are highly phagocytic and have a suppressive phenotype marked by an increase of alternatively activated macrophage markers, CD163 and macrophage scavenger receptor 1 (MRS1) [3, 5]. The macrophage phenotype that predominates in multibacillary patients contributes to bacterial survival and persistence inside cells by an IL-10-mediated pathway [2, 6]
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