Distinct Roles of Th17 and Th1 Cells in Inflammatory Responses Associated with the Presentation of Paucibacillary Leprosy and Leprosy Reactions

Abstract

It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4 T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous leprosy (LL) patients. Secondly, inflammatory cytokines were measured by multiplex assay of serum samples from Multibacillary (MB, n = 28) and Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23). Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n = 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed by flow cytometry used to determine the phenotype of cytokine-producing cells. Lesions from TT patients were found to have more CD4 IL-17A cells than those from LL patients. Higher concentrations of IL-17A and IL-1β were observed in serum from PB than MB patients. The highest serum IFN-γ concentrations were, however, detected in sera from MB patients that developed leprosy reactions (MB LR ). Together, these results indicate that Th1 cells were associated with both the PB presentation and also with leprosy reactions. In contrast, Th17 cells were associated with an effective inflammatory response that is present in the PB forms but were not predictive of leprosy reactions in MB patients.

Mycobacterium leprae Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy

“…We did identify elevated IL-17A levels in WBA with HHC than those using MB samples. A previous study by our group found an association of Th17 response with the milder PB forms of leprosy (16). Taken together, our data indicate a broader and more robust anti-mycobacterial immune response in HHC than that of patients.…”

“…There is now strong associative evidence that the genetic background and immunological response of the infected individual influence both susceptibility to M. leprae infection and outcome of leprosy (2, 4, 8, 9). Antigen-specific T helper 1 (Th1) and T helper 17 (Th17) cells are observed in paucibacillary (PB) patients and are associated with control of M. leprae replication (2, 8–16). In contrast, T helper 2 (Th2) and T regulatory (Treg) cells are associated with the multibacillary (MB) presentations that are characterized by heavily infected macrophages and multiple skin lesions (14, 15, 17).…”

Inflammatory cytokines in leprosy reactions and periodontal diseases

“…Santos et al . 10 observed that reactional multibacillary patients presented highest concentrations of serum IFN-γ. Likewise, Motta et al .…”

“…Appropriate innate and adaptive immune response interactions can influence the clinical outcome of leprosy, and recent studies suggest that higher serum IFN-γ concentrations are related to the development of leprosy reactions in individuals with the multibacillary form 10 , 11 .…”

Correlation of Hematological Parameters on Maternal and Pediatric Leprosy ImmunityRatio: A Study in Endemic Areas in East Java, Indonesia

“…5 The termination of leprosy transmission depends on several aspects such as microbiological aspects, environmental factors, and immunological aspect. 7,8 A good immune system needs to be nourished from the beginning of life by improving perinatal health status of both mother and child. 5 Previously, four subset of T cells, namely Th1, Th2, Th17, and Treg were known to play roles in human immune response against leprosy.…”