Absence of C-Maf and IL-10 Enables Type I IFN Enhancement of Innate Responses to Low-dose LPS in Alveolar Macrophages

Overview

Journal bioRxiv

Date 2024 Jun 3

PMID 38826239

Authors

Pamelia N Lim

Maritza M Cervantes

Linh K Pham

Sydney Doherty

Ankita Tufts

Divya Dubey

Dat Mai

Alan Aderem

Alan H Diercks

Alissa C Rothchild

Affiliations

Soon will be listed here.

Abstract

Alveolar macrophages (AMs) are lower-airway resident myeloid cells and are among the first to respond to inhaled pathogens. Here, we interrogate AM innate sensing to Pathogen Associated Molecular Patterns (PAMPs) and determine AMs have decreased responses to low-dose LPS compared to other macrophages, as measured by TNF, IL-6, , and . We find the reduced response to low-dose LPS correlates with minimal TLR4 and CD14 surface expression, despite sufficient internal expression of TLR4. Additionally, we find that AMs do not produce IL-10 in response to a variety of PAMPs due to low expression of transcription factor c-Maf and that lack of IL-10 production contributes to an enhancement of pro-inflammatory responses by Type I IFN. Our findings demonstrate that AMs have cell-intrinsic dampened responses to LPS, which is enhanced by type I IFN exposure. These data implicate conditions where AMs may have reduced or enhanced sentinel responses to bacterial infections.

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