title: Neither primary nor memory immunity to Mycobacterium tuberculosis infection is compromised in mice with chronic enteric helminth infection.
abstract: Previously we had reported that Nippostrongylus brasiliensis, a helminth with a lung migratory phase, affected host resistance against Mycobacterium tuberculosis infection through the induction of alternatively activated (M2) macrophages. Several helminth species do not have an obligatory lung migratory phase but establish chronic infections in the host that include potent immune downregulatory effects, in part mediated through induction of a FoxP3(+) T regulatory cell (Treg) response. Treg cells exhibit duality in their functions in host defense against M. tuberculosis infection since their depletion leads to enhanced priming of T cells in the lymph nodes and attendant improved control of M. tuberculosis infection, while their presence in the lung granuloma protects against excessive inflammation. Heligmosomoides polygyrus is a strictly murine enteric nematode that induces a strong FoxP3 Treg response in the host. Therefore, in this study we investigated whether host immunity to M. tuberculosis infection would be modulated in mice with chronic H. polygyrus infection. We report that neither primary nor memory immunity conferred by Mycobacterium bovis BCG vaccination was affected in mice with chronic enteric helminth infection, despite a systemic increase in FoxP3(+) T regulatory cells. The findings indicate that anti-M. tuberculosis immunity is not similarly affected by all helminth species and highlight the need to consider this inequality in human coinfection studies.
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Wasiulla
authors.initials: W
authors.lastname: Rafi
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Bhatt
authors.affiliation: Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Gause
authors.affiliation: Department of Medicine, Center for Emerging Pathogens, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey, USA salgampa@njms.rutgers.edu.
authors.forename: Padmini
authors.initials: P
authors.lastname: Salgame
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D060085:Coinfection; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D007113:Immunity, Innate; D007156:Immunologic Memory; D008168:Lung / Q000276:immunology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009164:Mycobacterium Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009351:Nematospiroides dubius / Q000276:immunology; D017206:Strongylida Infections / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D014611:Vaccination
chemical_list: D001500:BCG Vaccine; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse