The food-borne pathogen Listeria monocytogenes is adapted to a diversity of environments, such as soil, food, body fluids, and the cytosol of eukaryotic cells. The transition between saprophytic and pathogenic life is mediated through complex regulatory pathways that modulate the expression of virulence factors. Here we examined the expression of inlJ , a recently identified gene encoding a protein of the LPXTG-internalin family and involved in pathogenesis. We show that inlJ expression is controlled neither by the major listerial regulator of virulence genes, PrfA, nor by AxyR, a putative AraC regulator encoded by a gene adjacent to inlJ and divergently transcribed. The InlJ protein is not produced by bacteria grown in vitro in brain heart infusion medium or replicating in the cytosol of tissue-cultured cells. In contrast, it is efficiently produced and localized at the surface of bacteria present in the liver and blood of infected animals. Strikingly, the expression of inlJ by a heterologous promoter in L . monocytogenes or L . innocua promotes bacterial adherence to human cells in vitro. Taken together, these results strongly suggest that InlJ acts as a novel L . monocytogenes sortase-anchored adhesin specifically expressed during infection in vivo.

The genome of the pathogenic bacteriumListeria monocytogenescontains a family of genes encoding proteins with a leucine-rich repeat domain. One of these genes,inlH, is a σ^B-dependent virulence gene of unknown function. Previously,inlHwas proposed to be coexpressed with two adjacent internalin genes,inlGandinlE. Using tiling arrays, we showed thatinlHexpression is monocistronic and specifically induced in stationary phase as well as in the intestinal lumen of mice, independent ofinlGandinlEexpression. Consistent withinlHσ^B-dependent regulation, surface expression of the InlH protein is induced when bacteria are subjected to thermal, acidic, osmotic, or oxidative stress. Disruption ofinlHincreases the amount of the invasion protein InlA without changinginlAtranscript level, suggesting that there is a link betweeninlHexpression andinlAposttranscriptional regulation. However, in contrast to InlA, InlH does not contribute to bacterial invasion of cultured cellsin vitroor of intestinal cellsin vivo. Strikingly, the reduced virulence ofinlH-deficientL. monocytogenesstrains is accompanied by enhanced production of interleukin-6 (IL-6) in infected tissues during the systemic phase of murine listeriosis but not by enhanced production of any other inflammatory cytokine tested. Since InlH does not modulate IL-6 secretion in macrophages at leastin vitro, it may play a role in other immune cells or contribute to a pathway that modulates survival or activation of IL-6-secreting cells. These results strongly suggest that InlH is a stress-induced surface protein that facilitates pathogen survival in tissues by tempering the inflammatory response.