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B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response

Kozakiewicz, L and Chen, Y and Xu, J and Porcelli, SA and Jacobs, WR and Chan, J and Wang, Y and Dunussi-Joannopoulos, K and Ou, Q and Flynn, JL (2013) B Cells Regulate Neutrophilia during Mycobacterium tuberculosis Infection and BCG Vaccination by Modulating the Interleukin-17 Response. PLoS Pathogens, 9 (7). ISSN 1553-7366

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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. © 2013 Kozakiewicz et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kozakiewicz, L
Chen, Y
Xu, J
Porcelli, SA
Jacobs, WR
Chan, J
Wang, Y
Dunussi-Joannopoulos, K
Ou, Q
Flynn, JLjoanne@pitt.eduJOANNE
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSassett, Christopher M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 July 2013
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 9
Number: 7
DOI or Unique Handle: 10.1371/journal.ppat.1003472
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
ISSN: 1553-7366
Other ID: NLM PMC3708864
PubMed Central ID: PMC3708864
PubMed ID: 23853593
Date Deposited: 12 Aug 2013 19:13
Last Modified: 25 Jan 2019 20:55
URI: http://d-scholarship.pitt.edu/id/eprint/19500

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