A Bacterial Protein Targets the BAHD1 Chromatin Complex to Stimulate Type III Interferon Response

Abstract

Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate interferon (IFN)-stimulated genes (ISGs). IFN-λ expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1(+/-) mice or when lntA was constitutively expressed. Thus, the LntA-BAHD1 interplay may modulate IFN-λ-mediated immune response to control bacterial colonization of the host.

Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2

“…Additionally, Trp53 can direct E2f2-mediated growth arrest involving the target gene Gadd45. 40 E2f2 and Gadd45 are two genes that were upregulated in the Salmonella-susceptible B6.MOLF-Ity/ Ity2.RecD congenic strain, which further supports the [41][42][43] We showed here that Trp53 expression is affected by specific Ity2A genomic context, and we speculate that its impact on resistance to Salmonella infection is explained by favoring a cell-cycle arrest state allowing the bacteria to proliferate more successfully. Therefore, we conclude that the MOLF/Ei allele at Ity2 maintains the levels of Trp53 expression within a range that allows control of bacterial growth during infection, a situation that is beneficial to the host.…”

The arsenal of virulence factors deployed byListeria monocytogenesto promote its cell infection cycle

“…The mechanism allows the bacterium to govern both the induction and repression of the host cell immune response, perhaps to optimize conditions for specific stages of infection or colonization of specific tissues. 214 Besides the LLO functions above described (see vacuole escape section), LLO is also required for upregulation of adhesion molecules and chemokines in endothelial cells infected by L. monocytogenes. 123 LLO was also shown to be critical for dephosphorylation of histone H3 and deacetylation of histone H4, during the early phase of infection, 215 through a mechanism that involves LLO-induced pore-dependent efflux of potassium ions.…”

Listeria monocytogenesinduces host DNA damage and delays the host cell cycle to promote infection

“…33 Lm modifies host gene expression via 2 virulence factors, LntA and LLO. [20][21][22]34 LLO modulates host transcription from the extracellular milieu and is degraded once Lm escapes the vacuole, being unlikely to modify host histones from the cytoplasm. 20 Our data do not support a crucial role for LLO or any other bacterial secreted proteins acting from the extracellular milieu.…”

“…19 The interplay between Lm and the host cell cycle is understudied. Albeit Lm remains mostly cytosolic, it interferes with histone modifications 20,21 and chromatin-regulatory factors 22 to modulate host gene expression.…”