title: B cells regulate neutrophilia during Mycobacterium tuberculosis infection and BCG vaccination by modulating the interleukin-17 response.
abstract: We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, the Bronx, New York, New York, United States of America.
authors.forename: Lee
authors.initials: L
authors.lastname: Kozakiewicz
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Jiayong
authors.initials: J
authors.lastname: Xu
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Kyri
authors.initials: K
authors.lastname: Dunussi-Joannopoulos
authors.forename: Qinglin
authors.initials: Q
authors.lastname: Ou
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Flynn
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: John
authors.initials: J
authors.lastname: Chan
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D004423:Ear; D005260:Female; D056724:Immunity, Humoral; D007116:Immunization, Passive; D007271:Injections, Intradermal; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control; D015854:Up-Regulation
chemical_list: D001500:BCG Vaccine; C098680:Il17a protein, mouse; D020381:Interleukin-17