Reduced immunopathology and mortality despite tissue persistence in a Mycobacterium tuberculosis mutant lacking alternative σ factor, SigH

摘要: The pathogenesis of tuberculosis involves multiple phases and is believed to involve both a carefully deployed series adaptive bacterial virulence factors inappropriate host immune responses that lead tissue damage. A defined Mycobacterium mutant strain lacking the sigH-encoded transcription factor showed distinctive infection phenotype. In resistant C57BL/6 mice, achieved high counts in lung spleen persisted tissues pattern identical those wild-type bacteria. Despite burden, produced blunted, delayed pulmonary inflammatory response, recruited fewer CD4+ CD8+ T cells early stages infection. susceptible C3H again diminished immunopathology was nonlethal at over 170 days after intravenous infection, contrast isogenic bacilli, which killed with median time death 52 days. Complete genomic microarray analysis revealed M. sigH may mediate least 31 genes directly it modulates expression about 150 others; SigH regulon governs thioredoxin recycling be involved maintenance intrabacterial reducing capacity. These data show gene dispensable for growth survival within host, but required production lethality. This phenotype demonstrates beyond an ability grow persist has distinct mechanisms elicit deleterious progressive disease.