Attenuation of toll-like receptor expression and function in latent tuberculosis by coexistent filarial infection with restoration following antifilarial chemotherapy.

Babu, S.; Bhat, S.Q.; Kumar, N.P.; Anuradha, R.; Kumaran, P.; Gopi, P.G.; Kolappan, C.; Kumaraswami, V.; Nutman, T.B.

PLoS Neglected Tropical Diseases; 2009; 3; 1-8.

bstract: Mycobacterium tuberculosis (Mtb) and filarial coinfection is highly prevalent, and the presence of filarial infections may regulate the Toll-like receptor (TLR)-dependent immune response needed to control Mtb infection. By analyzing the baseline and mycobacterial antigen–stimulated expression of TLR1, 2, 4, and 9 (in individuals with latent tuberculosis [TB] with or without filarial infection), we were able to demonstrate that filarial infection, coincident with Mtb, significantly diminishes both baseline and Mtb antigen-specific TLR2 and TLR9 expression. In addition, pro-inflammatory cytokine responses to TLR2 and 9 ligands are significantly diminished in filaria/TB-coinfected individuals. Definitive treatment of lymphatic filariasis significantly restores the pro-inflammatory cytokine responses in individuals with latent TB. Coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific TLR-mediated immune responses in latent tuberculosis and suggests a novel mechanism by which concomitant filarial infections predispose to the development of active tuberculosis in humans.

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