PMID- 38496427 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240327 DP - 2024 Mar 5 TI - Salmonella Typhimurium infection inhibits macrophage IFNbeta signaling in a TLR4-dependent manner. LID - 2024.03.05.583530 [pii] LID - 10.1101/2024.03.05.583530 [doi] AB - Type I Interferons (IFNs) generally have a protective role during viral infections, but their function during bacterial infections is dependent on the bacterial species. Legionella pneumophila, Shigella sonnei and Mycobacterium tuberculosis can inhibit type I IFN signaling. Here we examined the role of type I IFN, specifically IFNbeta, in the context of Salmonella enterica serovar Typhimurium (STm) macrophage infections and the capacity of STm to inhibit type I IFN signaling. We demonstrate that IFNbeta has no effect on the intracellular growth of STm in infected bone marrow derived macrophages (BMDMs) derived from C57BL/6 mice. STm infection inhibits IFNbeta signaling but not IFNgamma signaling in a murine macrophage cell line. We show that this inhibition is independent of the type III and type VI secretion systems expressed by STm and is also independent of bacterial phagocytosis. The inhibition is Toll-like receptor 4 (TLR4)-dependent as the TLR4 ligand, lipopolysaccharide (LPS), alone is sufficient to inhibit IFNbeta-mediated signaling and STm-infected, TLR4-deficient BMDMs do not exhibit inhibited IFNbeta signaling. In summary, we show that macrophages exposed to STm have reduced IFNbeta signaling via crosstalk with TLR4 signaling, and that IFNbeta signaling does not affect cell autonomous host defense against STm. FAU - Shuster, Michael AU - Shuster M AUID- ORCID: 0000-0002-6861-8398 AD - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. FAU - Lyu, Zhihui AU - Lyu Z AD - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. FAU - Augenstreich, Jacques AU - Augenstreich J AUID- ORCID: 0000-0003-2147-2675 AD - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. FAU - Mathur, Shrestha AU - Mathur S AD - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. FAU - Ganesh, Akshaya AU - Ganesh A AD - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. FAU - Ling, Jiqiang AU - Ling J AUID- ORCID: 0000-0003-4466-8304 AD - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. FAU - Briken, Volker AU - Briken V AUID- ORCID: 0000-0001-5830-6107 AD - Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA. LA - eng GR - R21 AI142396/AI/NIAID NIH HHS/United States GR - R01 AI139492/AI/NIAID NIH HHS/United States GR - R35 GM136213/GM/NIGMS NIH HHS/United States GR - T32 GM080201/GM/NIGMS NIH HHS/United States GR - S10 OD025223/OD/NIH HHS/United States PT - Preprint DEP - 20240305 PL - United States TA - bioRxiv JT - bioRxiv : the preprint server for biology JID - 101680187 PMC - PMC10942315 EDAT- 2024/03/18 06:42 MHDA- 2024/03/18 06:43 PMCR- 2024/03/15 CRDT- 2024/03/18 04:37 PHST- 2024/03/18 06:42 [pubmed] PHST- 2024/03/18 06:43 [medline] PHST- 2024/03/18 04:37 [entrez] PHST- 2024/03/15 00:00 [pmc-release] AID - 2024.03.05.583530 [pii] AID - 10.1101/2024.03.05.583530 [doi] PST - epublish SO - bioRxiv [Preprint]. 2024 Mar 5:2024.03.05.583530. doi: 10.1101/2024.03.05.583530.