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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
S100A8/A9 proteins mediate neutrophilic inflammation and lung pathology during tuberculosis
American Journal of Respiratory and Critical Care Medicine, Volume 188, No. 9, Year 2013
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Description
Rationale:Ahallmark of pulmonary tuberculosis (TB) is the formation of granulomas. However, the immune factors that drive the formation of a protective granuloma during latent TB, and the factors that drive the formation of inflammatory granulomas during active TB, are not well defined. Objectives: The objective of this study was to identify the underlying immune mechanisms involved in formation of inflammatory granulomas seen during active TB. Methods: The immune mediators involved in inflammatory granuloma formation during TB were assessed using human samples and experimental models of Mycobacterium tuberculosis infection, using molecular and immunologic techniques. Measurements and Main Results: We demonstrate that in human patients with active TB and in nonhuman primatemodels of M. tuberculosis infection, neutrophils producing S100 proteins are dominantwithin the inflammatory lung granulomas seen during active TB. Using themouse model of TB, we demonstrate that the exacerbated lung inflammation seenasaresultofneutrophilicaccumulation isdependentonS100A8/A9 proteins. S100A8/A9 proteins promote neutrophil accumulation by inducing production of proinflammatory chemokines and cytokines, and influencing leukocyte trafficking. Importantly, serum levels of S100A8/ A9 proteins along with neutrophil-associated chemokines, such as keratinocytechemoattractant, canbeusedaspotential surrogatebiomarkers to assess lung inflammation and disease severity in human TB. Conclusions: Our results thus show a major pathologic role for S100A8/A9 proteins in mediating neutrophil accumulation and inflammation associated with TB. Thus, targeting specific molecules, such as S100A8/A9proteins, has the potential to decrease lung tissue damage without impacting protective immunity against TB. Copyright © 2013 by the American Thoracic Society.
Authors & Co-Authors
Gopal, Radha
United States, Jamaica
Division of Infectious Diseases
Monin, Leticia
United States, Jamaica
Division of Infectious Diseases
Torres, Diana
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Slight, Samantha
United States, Jamaica
Division of Infectious Diseases
Mehra, Smriti
United States, Covington
Tulane National Primate Research Center
McKenna, Kyle C.
United States, Philadelphia
Eye and Ear Institute
Junecko, Beth A.Fallert
United States, Pittsburgh
University of Pittsburgh
Reinhart, Todd A.
United States, Pittsburgh
University of Pittsburgh
Kolls, Jay K.
United States, Pittsburgh
University of Pittsburgh School of Medicine
Báez-Saldańa, Renata
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Cruz-Lagunas, Alfredo
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Rodríguez-Reyna, Tatiana S.
Mexico, Tlalpan
Instituto Nacional de la Nutrición Salvador Zubiran
Kumar, Nathella Pavan
India, New Delhi
National Institute of Fashion Technology India
Tessier, Phillipe
Canada, Quebec
Université Laval
Roth, Johannes
Germany, Munster
University of Münster
Selman-Lama, Moisés E.
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Becerril-Villanueva, Enrique
Mexico, Mexico
Instituto Nacional de Psiquiatría Ramon de la Fuente
Baquera-Heredia, Javier
Mexico
American British Cowdray Medical Center
Cumming, Bridgette M.
South Africa, Durban
Africa Health Research Institute
Kasprowicz, Victoria O.
South Africa, Durban
Africa Health Research Institute
United States, Cambridge
Massachusetts Institute of Technology
South Africa, Durban
The Nelson R. Mandela Medical School
Steyn, Adrie J.C.
South Africa, Durban
Africa Health Research Institute
United States, Birmingham
The University of Alabama at Birmingham
Babu, Subash S.
India, New Delhi
National Institute of Fashion Technology India
Kaushal, Deepak
United States, Covington
Tulane National Primate Research Center
Zúñiga, Joaquín
Mexico, Tlalpan
Instituto Nacional de Enfermedades Respiratorias
Vogl, Thomas Josef
Germany, Munster
University of Münster
Rangel-Moreno, Javier
United States, Rochester
University of Rochester Medical Center
Khader, Shabaana Abdul
United States, Jamaica
Division of Infectious Diseases
United States, St. Louis
Washington University in St. Louis
Statistics
Citations: 27
Authors: 27
Affiliations: 18
Identifiers
Doi:
10.1164/rccm.201304-0803OC
ISSN:
1073449X
Research Areas
Infectious Diseases