title: Attenuation of toll-like receptor expression and function in latent tuberculosis by coexistent filarial infection with restoration following antifilarial chemotherapy.
abstract: 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.
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai, India. sbabu@mail.nih.gov
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
authors.forename: Sajid Q
authors.initials: SQ
authors.lastname: Bhat
authors.forename: N Pavan
authors.initials: NP
authors.lastname: Kumar
authors.forename: R
authors.initials: R
authors.lastname: Anuradha
authors.forename: Paul
authors.initials: P
authors.lastname: Kumaran
authors.forename: P G
authors.initials: PG
authors.lastname: Gopi
authors.forename: C
authors.initials: C
authors.lastname: Kolappan
authors.forename: V
authors.initials: V
authors.lastname: Kumaraswami
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005368:Filariasis / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D005369:Filaricides / Q000627:therapeutic use*; D005370:Filarioidea / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D055985:Latent Tuberculosis / Q000150:complications* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D051193:Toll-Like Receptors / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D016207:Cytokines; D005369:Filaricides; D051193:Toll-Like Receptors