Human Type 1 and 17 Responses in Latent Tuberculosis Are Modulated by Coincident Filarial Infection through Cytotoxic T Lymphocyte Antigen–4 and Programmed Death–1

Babu, Subash and Bhat, S Q and Pavan Kumar, S and Jayantasri, S and Rukmani, S and Paul Kumaran, P and Gopi, P G and Kolappan, C and Kumaraswami, V and Nutman, T B (2009) Human Type 1 and 17 Responses in Latent Tuberculosis Are Modulated by Coincident Filarial Infection through Cytotoxic T Lymphocyte Antigen–4 and Programmed Death–1. Journal of Infectious Diseases, 200 (2). pp. 288-298. ISSN Print 0022-1899; Online 1537-6613

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Abstract

Mycobacterium tuberculosis and filarial coinfection is highly prevalent, and the presence of a tissue-invasive helminth may modulate the predominant type 1 T helper (Th1; interferon [IFN]–g–mediated) response needed to control M. tuberculosis infection. By analyzing the cellular responses to mycobacterial antigens in patients who had latent tuberculosis with or without filarial infection, we were able to demonstrate that filarial infection coincident with M. tuberculosis infection significantly diminishes M. tuberculosis–specific Th1 (interleukin [IL]–12 and IFN-g) and type 17 T helper (Th17; IL-23 and IL-17) responses related to increased expression of cytotoxic T lymphocyte antigen (CTLA)–4 and programmed death (PD)–1. Blockade of CTLA-4 restored production of both IFN-g and IL-17, whereas PD-1 blockade restored IFN-g production only. Thus, coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific Th1 and Th17 responses in latent tuberculosis, suggesting a mechanism by which concomitant filarial (and other systemic helminth) infections predispose to the development of active tuberculosis in humans.

Item Type: Article
Uncontrolled Keywords: Latent Tuberculosis; Filariasis; Filarial; Cytitoxic T Lymphocyte
Subjects: Tuberculosis > Laboratory Research > Immunological
Filariasis
Tuberculosis
Divisions: Basic Science Research > Immunology
Depositing User: Rathinasabapati R
Date Deposited: 14 Nov 2017 09:25
Last Modified: 14 Nov 2017 09:25
URI: http://eprints.nirt.res.in/id/eprint/958

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