title: Modulation of mycobacterial-specific Th1 and Th17 cells in latent tuberculosis by coincident hookworm infection.
abstract: Hookworm infections and tuberculosis (TB) are coendemic in many parts of the world. It has been suggested that infection with helminth parasites could suppress the predominant Th1 (IFN-γ-mediated) response needed to control Mycobacterium tuberculosis infection and enhance susceptibility to infection and/or disease. To determine the role of coincident hookworm infection on responses at steady-state and on M. tuberculosis-specific immune responses in latent TB (LTB), we examined the cellular responses in individuals with LTB with or without concomitant hookworm infection. By analyzing the expression of Th1, Th2, and Th17 subsets of CD4(+) T cells, we were able to demonstrate that the presence of coincident hookworm infection significantly diminished both spontaneously expressed and M. tuberculosis-specific mono- and dual-functional Th1 and Th17 cells. Hookworm infection, in contrast, was associated with expanded frequencies of mono- and dual-functional Th2 cells at both steady-state and upon Ag stimulation. This differential induction of CD4(+) T cell subsets was abrogated upon mitogen stimulation. Additionally, coincident hookworm infection was associated with increased adaptive T regulatory cells but not natural regulatory T cells in LTB. Finally, the CD4(+) T cell cytokine expression pattern was also associated with alterations in the systemic levels of Th1 and Th2 cytokines. Thus, coincident hookworm infection exerts a profound inhibitory effect on protective Th1 and Th17 responses in LTB and may predispose toward the development of active tuberculosis in humans.
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, Chennai 600031, India.
authors.forename: Parakkal Jovvian
authors.initials: PJ
authors.lastname: George
authors.forename: Rajamanickam
authors.initials: R
authors.lastname: Anuradha
authors.forename: Paramasivam Paul
authors.initials: PP
authors.lastname: Kumaran
authors.forename: Vedachalam
authors.initials: V
authors.lastname: Chandrasekaran
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000328:Adult; D000368:Aged; D000723:Ancylostomatoidea / Q000276:immunology; D000818:Animals; D005243:Feces / Q000469:parasitology; D005260:Female; D006725:Hookworm Infections / Q000150:complications / Q000276:immunology*; D006801:Humans; D055985:Latent Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D058504:Th17 Cells / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D018418:Th2 Cells / Q000276:immunology* / Q000382:microbiology / Q000469:parasitology; D055815:Young Adult