title: 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.
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]-gamma-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-gamma) 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-gamma and IL-17, whereas PD-1 blockade restored IFN-gamma 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.
authors.affiliation: National Institutes of Health - International Center for Excellence in Research, 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: S
authors.initials: S
authors.lastname: Jayantasri
authors.forename: S
authors.initials: S
authors.lastname: Rukmani
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: D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D060908:CTLA-4 Antigen; D005260:Female; D005368:Filariasis / Q000150:complications* / Q000276:immunology*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D061026:Programmed Cell Death 1 Receptor; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology; D014376:Tuberculosis / Q000150:complications* / Q000276:immunology*; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D020381:Interleukin-17; D053759:Interleukin-23; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma