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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
The phenolic glycolipid of Mycobacterium tuberculosis differentially modulates the early host cytokine response but does not in itself confer hypervirulence
Infection and Immunity, Volume 76, No. 7, Year 2008
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Description
Mycobacterium tuberculosis possesses a diversity of potential virulence factors including complex branched lipids such as the phenolic glycolipid PGL-tb. PGL-tb expression by the clinical M. tuberculosis isolate HN878 has been associated with a less efficient Th1 response and increased virulence in mice and rabbits. It has been suggested that the W-Beijing family is the only group of M. tuberculosis strains with an intact pks1-15 gene, required for the synthesis of PGL-tb and capable of producing PGL-tb. We have found that some strains with an intact pks1-15 do not produce PGL-tb while others may produce a variant of PGL-tb. We examined the early host cytokine response to infection with these strains in vitro to better understand the effect of PGL-tb synthesis on immune responses. In addition, we generated a PGL-tb-producing H37Rv in order to determine the effect of PGL-tb production on the host immune response during infection by a strain normally devoid of PGL-tb synthesis. We observed that PGL-tb production by clinical M. tuberculosis isolates affected cytokine production differently depending on the background of the strain. Importantly, while ectopic PGL-tb production by H37Rv suppressed the induction of several pro- and anti-inflammatory cytokines in vitro in human monocytes, it did not lead to increased virulence in infected mice and rabbits. Collectively, our data indicate that, while PGL-tb may play a role in the immunogenicity and/or virulence of M. tuberculosis, it probably acts in concert with other bacterial factors which seem to be dependent on the background of the strain. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Sinsimer, Daniel
United States, Newark
Public Health Research Institute
United States, New Brunswick
School of Graduate Studies
Huet, Gaelle
France, Toulouse
Ipbs Institut de Pharmacologie et de Biologie Structurale
Manca, Claudia
United States, Newark
Public Health Research Institute
Tsenova, Liana
United States, Newark
Public Health Research Institute
Koo, Mi Sun
United States, Newark
Public Health Research Institute
Kurepina, Natalia E.
United States, Newark
Public Health Research Institute
Kana, Bavesh Davandra
South Africa, Johannesburg
School of Pathology
Mathema, Barun
United States, Newark
Public Health Research Institute
Marras, Salvatore A.E.
United States, Newark
Public Health Research Institute
Kreiswirth, Barry N.
United States, Newark
Public Health Research Institute
Guilhot, Christophe
France, Toulouse
Ipbs Institut de Pharmacologie et de Biologie Structurale
Kaplan, Gilla
United States, Newark
Public Health Research Institute
Statistics
Citations: 134
Authors: 12
Affiliations: 4
Identifiers
Doi:
10.1128/IAI.01663-07
ISSN:
00199567
Research Areas
Genetics And Genomics
Infectious Diseases