{"doi":"10.1165/rcmb.2023-0098ed","title":"Alveolar Macrophages during Inflammation: A Balancing Act","abstract":"A Balancing ActSepsis is a systemic inflammatory syndrome caused by a dysregulation of host response to infection that can lead to multipleorgan dysfunction and death.Although advances in protocolized sepsis management have substantially decreased early mortality, sepsis survivors can still exhibit protracted clinical courses characterized by recurrent or persistent secondary infections and organ dysfunction (1).The contribution of the primary site of infection, pathogen specificity, and molecular mechanisms underlying this \"persistent critical illness\" phenotype following sepsis are incompletely understood (2).However, a growing body of literature supports a complex interplay of proinflammatory and immunosuppressive mechanisms causing functional reprogramming of innate and adaptive immune cell subsets to drive immunopathology (1, 3).Specifically, the loss of effector function and increased expression of inhibitory molecules by monocytes, macrophages, and T cells, coupled with decreased expression of activating major histocompatibility complex II molecules by antigen-presenting cells, are among the most prominent features of sepsis-induced immunosuppression (3).Long-lived alveolar macrophages (AM) exert myriad functions to maintain tissue integrity and orchestrate acute responses to lung inflammation, injury, and repair.These specialized phagocytes establish intercellular signaling pathways in the lung microenvironment to effectively clear pathogens and facilitate noninflammatory removal of apoptotic cells following pulmonary infection (4).In this issue of the Journal, Llitjos and colleagues (pp.689-701) report on a study that used a double-infection experimental model to investigate the contribution of primary sepsis etiology to susceptibility to secondary bacterial pneumonia (5).Notably, they found that mice with cecal ligation and puncture (CLP)-induced polymicrobial peritonitis exhibit worsened mortality and decreased bacterial clearance from secondary Pseudomonas aeruginosa (PA) compared with animals initially challenged with Escherichia coli-induced pneumonia.Lung-specific immune cell subset analysis throughout the course of primary infection revealed a sequential and significant increase in Ly6C hi classical monocytes and AMs in the E. coli pneumonia group compared with the CLP-treated group, respectively.Measurement of the phagocytic and antigen-presenting capacity of AMs, combined with flow-cytometry analysis of activation and antiinflammatory markers and transcriptional profiling of AM following primary and secondary infection, led the authors to hypothesize that changes in AM numbers and function inform the divergent susceptibility to secondary lung PA infection.Functional analysis showed that post-E.coli pneumonia AMs exhibit increased expression of lipid metabolic processes compared with post-CLP","journal":"American Journal of Respiratory Cell and Molecular Biology","year":2023,"id":383168,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":289274,"name":"Luisa Morales‐Nebreda","orcid":"0000-0002-7126-0518","position":1,"is_corresponding":false},{"id":618012,"name":"Taylor A. Poor","orcid":"0000-0002-2191-5037","position":0,"is_corresponding":true}],"reference_count":17,"raw_metadata":null,"created_at":"2026-07-19T01:17:25.158896Z","pmid":"37022093","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}