help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Published ahead of print on April 25, 2008
Am. J. Respir. Cell Mol. Biol. 2008, doi:10.1165/rcmb.2007-0413OC
This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Sampaio, E. P
Right arrow Articles by Holland, S. M
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sampaio, E. P
Right arrow Articles by Holland, S. M

Submitted on November 13, 2007
Revised on April 24, 2008

M. abscessus and M. avium Trigger Toll like Receptor 2 and Distinct Cytokine Response in Human Cells

Elizabeth P Sampaio1*, Houda Z Elloumi2, Adrian Zelazny2, Li Ding2, Michelle L Paulson2, Alan Sher3, Andre L Bafica4, Yvonne R Shea5, and Steve M Holland2

1 Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA; Leprosy Laboratory, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Rio de Janeiro, Brazil, 2 Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA, 3 Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA, 4 Immunobiology Section, Laboratory of Parasitic Diseases, NIAID, NIH, Bethesda, Maryland, USA; Division of Immunology, Department of Microbiology and Parasitology, Federal University of Santa Catarina, Florianopolis, Santa Catarina, Brazil, 5 Department of Laboratory Medicine, Clinical Center, NIH, Bethesda, Maryland, USA

* To whom correspondence should be addressed. E-mail: sampaioe{at}niaid.nih.gov.

Rationale: M. avium and M. abscessus are ubiquitous environmental organisms increasingly recognized to cause chronic lung disease in patients with apparently normal immune function. Little is yet known about their human pathophysiology. Objectives and Methods: To examine cytokine, chemokine responses (protein and gene expression) and signaling pathways triggered by reference and clinical isolates of M. abscessus and M. avium in human peripheral blood mononuclear cells, monocytes and murine bone marrow-derived macrophages in vitro. Results: M. abscessus-induced tumor necrosis factor alpha (TNF{alpha})production was higher than that induced by M. avium. Interferon-{gamma}, interleukin-1{beta}, and the chemokines macrophage inflammatory protein-1{alpha} and regulated on activation, normal T cell expressed and secreted (RANTES) were equally up-regulated. Differences between MAB and MAV do not require replication and are heat stable. We found no differential effect due to rough or smooth colonies within the same species. Similar to M. avium, M. abscessus triggered mitogen activated protein kinase (MAPK) signaling and nuclear factor-{kappa}B translocation. Induction of TNF{alpha} was dependent on MAPK pathways since pre-incubation of cells with signaling inhibitors led to >85% reduction in cytokine secretion. M. abscessus also triggered a Toll-like receptor 2 (TLR2)-mediated response that led to TNF{alpha} production by human monocytes. Accordingly, stimulation of murine TLR2- or myeloid differentiation factor 88-deficient bone marrow-derived macrophages did not elicit TNF{alpha}, reinforcing a critical role for TLR2 in M. abscessus-induced cell activation. Conclusion: M. abscessus signals human cells through MAPK and TLR2 pathways and triggers more pronounced pro-inflammatory cytokines and chemokines than M. avium.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 2008 American Thoracic Society.