This study identified the presence of MDSCs in patients with leprosy and its expression of ANXA1. This data was also correlated with the presence of the BCG vaccination scar and the bacilloscopy index to establish a possible default association in leprosy reactions.
The epidemiological data showed that men were the most affected in this study. These data are consistent with the findings reported in the literature [25–27]. Several factors contribute to this scenario: lower health care dispensed, lifestyle factors, less concern with the self. Altogether, it may contribute to late diagnosis and, subsequently, disease dissemination. Also, the data showed that the predominant skin color as brown is observed in other studies [25, 28]. Most of the participants were residents in the urban area, which is also corroborated in other studies [29].
Then, the presence of the BCG vaccination scar was evaluated. The majority of them have the BCG vaccination scar. However, it is not completely clear how efficient this vaccine can protect leprosy patients [30, 31]. Those with BCG scar presented a higher bacilloscopy index with bacilli (M. leprae) intact. Some studies postulate that genetic polymorphisms might be responsible for the immunological incapacity of protection [32].
Subsequently, the presence of MDSCs were reported in patients with leprosy. A higher number of MDSCs were observed in LL and T2R patients when compared to T1R ones. The literature suggested that infectious diseases might inhibit the maturation of myeloid cells in the bone marrow, inducing migration to the inflammatory site, and differentiation as suppressor cells [33]. The presence of these cells in patients LL alone can reduce the efficiency of the immunological system to fight against M. leprae. This data suggest that the fundamental role of MDSCs in the regulation of inflammatory reaction. Some studies say M-MDSC induces the proliferation of macrophages M2-like in hypoxic tumour areas [13] and contributes to the extracellular matrix remodelling [34]. Also, M-MDSC produces reactive oxygen species, which disrupts the T-cell function by modifying its TCR-ζ chain [16]. Regarding the G-MDSC, it mediates an immunosuppressive pattern through STAT6 signalling and expression of ARG-1 and TGF-β [8]. Also, G-MDSC induces the activation of Treg cells through IFN-γ and IL-10 [12].
The presence of M-MDSCs in high number was observed in the patients with LL and T2R patients with BCG vaccination scar. Some studies have described that the BCG vaccination or inoculation with M. tuberculosis antigens induce the MDSC migration [35, 36]. This data and other genetic polymorphisms might make those patients more susceptible to developing the worst symptoms of leprosy.
Finally, to analyze a possible mechanism of action of MDSCs in patients with leprosy, the ANXA1 expression was analyzed. Previous studies have already demonstrated the ANXA1 expression in leukocytes of leprosy patients [37, 38]. However, this is the first study that highlights the presence of this protein in MDSCs. The data showed that the ANXA1 levels found in M-MDSCs were higher in LL patients when compared to the T1R and T2R, while similar levels were observed in G-MDSC at all patients. The literature shows that the ANXA1 is an endogenous regulatory protein expressed at high concentrations in granulocytes, particularly neutrophils [39–42]. The lower levels of ANXA1 in M-MDSCs of T1R and T2R might be due to drug treatment. This result can be an important limitation of this work. In particular, literature shows that, after 24 h of glucocorticoids treatment, ANXA1 expression reduces in macrophages [40]. Therefore, the high levels of this protein, observed in G-MDSC, might be linked to the type of cell lineage. It is well known that the ANXA1 has a modulatory role in the innate and adaptive immune response. Studies with ANXA1 knockout animals show the acute and systemic inflammation exacerbation by pro-inflammatory TNF-α, IL-1β, and IL-6 release [17, 39, 40]. Also, ANXA1 is involved in the induction of IL-10 production (de Coupade et al., 2001; Parente and Solito, 2004; Damazo et al., 2005). This cytokine is produced by MDSCs and is an essential molecule in the immune system regulation. This data suggest that the high ANXA1 expression in MDSCs at LL and T2R patients may be related to the regulation of infectious response, reducing the effectiveness of T cells action, and establishing an anergic response, leading patient susceptible to M. leprae.
Clinical evolution of leprosy is directly involved with the participation of pro-inflammatory mediators, which direct the immune response to a cellular or humoral profile. Some of these have their role well elucidated in the literature, However, there are gaps related to issues of resistance or susceptibility to individuals exposed to the bacillus. It was demonstrated the presence and importance of MDSC that can influence the host response against leprosy. Many issues and challenges are still open for the research of MDSCs and their role in leprosy.