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Profiling early lung immune responses in the mouse model of tuberculosis

Kang, DD and Lin, Y and Moreno, JR and Randall, TD and Khader, SA (2011) Profiling early lung immune responses in the mouse model of tuberculosis. PLoS ONE, 6 (1).

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Abstract

Tuberculosis (TB) is caused by the intracellular bacteria Mycobacterium tuberculosis, and kills more than 1.5 million people every year worldwide. Immunity to TB is associated with the accumulation of IFNγ-producing T helper cell type 1 (Th1) in the lungs, activation of M.tuberculosis-infected macrophages and control of bacterial growth. However, very little is known regarding the early immune responses that mediate accumulation of activated Th1 cells in the M.tuberculosis-infected lungs. To define the induction of early immune mediators in the M.tuberculosis-infected lung, we performed mRNA profiling studies and characterized immune cells in M.tuberculosis-infected lungs at early stages of infection in the mouse model. Our data show that induction of mRNAs involved in the recognition of pathogens, expression of inflammatory cytokines, activation of APCs and generation of Th1 responses occurs between day 15 and day 21 post infection. The induction of these mRNAs coincides with cellular accumulation of Th1 cells and activation of myeloid cells in M.tuberculosis-infected lungs. Strikingly, we show the induction of mRNAs associated with Gr1+ cells, namely neutrophils and inflammatory monocytes, takes place on day 12 and coincides with cellular accumulation of Gr1+ cells in M.tuberculosis-infected lungs. Interestingly, in vivo depletion of Gr1+ neutrophils between days 10-15 results in decreased accumulation of Th1 cells on day 21 in M.tuberculosis-infected lungs without impacting overall protective outcomes. These data suggest that the recruitment of Gr1+ neutrophils is an early event that leads to production of chemokines that regulate the accumulation of Th1 cells in the M.tuberculosis-infected lungs.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kang, DD
Lin, Y
Moreno, JR
Randall, TD
Khader, SA
Date: 1 February 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 1
DOI or Unique Handle: 10.1371/journal.pone.0016161
Schools and Programs: School of Public Health > Biostatistics
Refereed: Yes
MeSH Headings: Animals; Cytokines--biosynthesis; Disease Models, Animal; Gene Expression Profiling; Immunity; Lung--immunology; Lung--microbiology; Lung--pathology; Mice; Mycobacterium tuberculosis; Neutrophil Infiltration; RNA, Messenger--analysis; Th1 Cells--immunology; Time Factors; Tuberculosis, Pulmonary--immunology; Tuberculosis, Pulmonary--pathology
Other ID: NLM PMC3020951
PubMed Central ID: PMC3020951
PubMed ID: 21249199
Date Deposited: 03 Aug 2012 18:49
Last Modified: 22 Jun 2021 11:55
URI: http://d-scholarship.pitt.edu/id/eprint/13253

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