ABSTRACT
BACKGROUND: Latent tuberculous infection (LTBI) can function as a 'reservoir' for Mycobacterium tuberculosis. Given that T-regulatory cell (Treg) numbers are augmented in LTBI, it is likely that Toll-like receptors (TLRs) may have a role in Treg function. Elucidation of the immune mechanisms associated with tuberculosis (TB) development may help to control M. tuberculosis spread.OBJECTIVE: To investigate the role of TLR2, TLR4 and TLR9 in hindered in vitro microbicidal activity and increase Treg number during LTBI. DESIGN: Whole blood cell cultures from individuals with LTBI and healthy controls (HCs) infected with live M. tuberculosis H37Rv strain were used to investigate the effect of TLR2, TLR4 and TLR9 on Treg number, microbicidal activity, and interferon-gamma and interleukin (IL)10 production. RESULTS: LTBI subjects were characterised by increased Treg number and impaired microbicidal activity when compared with HCs. Specific blockade of TLR4 and TLR9 led to a significant reduction in Treg number, a decrease in IL-10 production and substantial upregulation of microbicidal activity. CONCLUSION: M. tuberculosis infection may activate TLR4 and TLR9 pathways to suppress M. tuberculosis-specific immune responses. Here, we show that activation of TLR4 and TLR9 hinder microbicidal activity during LTBI.
Subject(s)
Latent Tuberculosis/immunology , Mycobacterium tuberculosis/immunology , Toll-Like Receptor 4/immunology , Toll-Like Receptor 9/immunology , Adult , Female , Humans , In Vitro Techniques , Interferon-gamma/immunology , Interleukin-10/immunology , Latent Tuberculosis/microbiology , Male , Middle Aged , T-Lymphocytes, Regulatory/immunology , Toll-Like Receptor 2/immunology , Young AdultABSTRACT
Previously, we described the protective action of the immunomodulatory extract of Kalanchoe pinnata (Kp) in murine and human cutaneous leishmaniasis. In the present study, we investigated the effectiveness of Kp against visceral leishmaniasis, using the BALB/c mouse model of infection with Leishmania chagasi. Mice receiving oral daily doses of Kp (400 mg/kg) for 30 days displayed significantly reduced hepatic and splenic parasite burden, when compared with untreated animals. Protectiveness was accompanied by a reduction in parasite-specific IgG serum levels, and impaired capacity of spleen cells to produce IL-4, but not IFN-gamma and nitric oxide upon antigen recall in vitro. The reference drug Pentostam (72 mg/kg) given by the intra-peritoneal route on alternate days produced an anti-leishmanial effect similar to oral Kp. Our findings show that the oral efficacy of Kp, seen previously in murine cutaneous leishmaniasis, extends also to visceral leishmaniasis caused by L. chagasi, a difficult to treat and lethal disease of man.
