attenuation of toll-like receptor expression and function in latent tuberculosis by coexistent filarial infection with restoration following antifilarial chemotherapy衰减潜伏性结核病的toll样受体表达和功能同时共存的丝虫的感染antifilarial化疗后恢复.pdf

Attenuation of Toll-Like Receptor Expression and Function in Latent Tuberculosis by Coexistent Filarial Infection with Restoration Following Antifilarial Chemotherapy 1,2 1 1 1 3 3 Subash Babu *, Sajid Q. Bhat , N. Pavan Kumar , R. Anuradha , Paul Kumaran , P. G. Gopi , 3 3 4 C. Kolappan , V. Kumaraswami , Thomas B. Nutman 1 National Institutes of Health—International Center for Excellence in Research, Chennai, India, 2 Science Applications International Corporation (SAIC)-Frederick, National Cancer Institute (NCI)–Frederick, Frederick, Maryland, United States of America, 3 Tuberculosis Research Center, Chennai, India, 4 Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America 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