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.

Mycobacterium tuberculosis‐specific CD4+ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB

“…Some studies have specifically demonstrated the importance of regulatory T cells in suppression of the immune response to BCG during helminth infection [32,33] and the modulation of the TB immune response during helminth infection [10,14,26]. A number of previous studies have investigated the immunomodulatory effect of helminth infections on antimycobacterial immunity [11,34]. In this study, we took advantage of an opportunity provided by a London cohort of immigrants who had presented with helminth infection with/without LTBI to evaluate the impact of deworming on the in vitro T-cell memory response to Mtb in these patients.…”

Tuberculosis Comorbidity with Communicable and Noncommunicable Diseases

“…Looking in more detail at components of the immune response, there is evidence for helminth-associated regulatory T cells suppressing responses to BCG (Bacillus Calmette-Guérin) vaccination in children (Wammes et al 2010) and Mtb-specific Toll-like receptor expression in adults (Babu et al 2009). Ex vivo studies in which monocytes differentiated into dendritic cells and macrophages, and then stimulated in vitro with live …”

Genomics of immune response to typhoid and cholera vaccines

“…TLR1 showed association with the host response to the vaccine. An important immune evasion mechanism in some bacterial pathogens is by downregulation of TLR-mediated immune responses through diminished TLR-mediated cell signalling or expression [33,34]. TLR1 coexpresses with CD86 (figure 2).…”