Open AccessThe Phenolic Glycolipid ofMycobacterium tuberculosisDifferentially Modulates the Early Host Cytokine Response but Does Not in Itself Confer Hypervirulence
Author(s) -
Daniel Sinsimer,
Gaëlle Huet,
Claudia Manca,
Liana Tsenova,
Mi Sun Koo,
Natalia Kurepina,
Bavesh D Kana,
Barun Mathema,
Salvatore A. E. Marras,
Barry N. Kreiswirth,
Christophe Guilhot,
Gilla Kaplan
Publication year - 2008
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.01663-07
Subject(s) - biology , virulence , mycobacterium tuberculosis , microbiology and biotechnology , tuberculosis , immune system , immunogenicity , cytokine , glycolipid , virology , immunology , gene , genetics , medicine , pathology
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 clinicalM. 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 ofM. tuberculosis strains with an intactpks1 -15 gene, required for the synthesis of PGL-tb and capable of producing PGL-tb. We have found that some strains with an intactpks1 -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 clinicalM. 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 ofM. tuberculosis , it probably acts in concert with other bacterial factors which seem to be dependent on the background of the strain.