Dataset Information

CD11b restricts alveolar macrophage activation during pneumococcal pneumonia and prevents excessive lung inflammation

ABSTRACT: Bacterial lung infections are associated with strong infiltration of CD11b+ myeloid cells, which limit life-threatening disease, but also severely damage lung tissue. In a murine lung infection model with Streptococcus pneumoniae, we found intrinsic upregulation of CD11b on resident alveolar macrophages. Such CD11b expression was associated with transcriptomic and proteomic adaptations by alveolar macrophages, leading to the identification of specific molecules and pathways that depended on CD11b. In the absence of CD11b, the antimicrobial defense of alveolar macrophages was strongly reduced, and the production of neutrophil-recruiting chemokines was more pronounced. Moreover, CD11b expression limited the infection and prevented excessive alveolar damage. In conclusion, our study provides detailed molecular insights into the alveolar macrophage-specific immune response to Streptococcus pneumoniae lung infection and reveals profound CD11b-dependent alterations that are critical for effective antimicrobial immunity, neutrophil recruitment, and prevention of alveolar damage.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Lung, Macrophage

DISEASE(S): Pneumonia

SUBMITTER: Thilo Bracht

LAB HEAD: Thilo Bracht

PROVIDER: PXD035269 | Pride | 2023-10-08

REPOSITORIES: Pride

ACCESS DATA

Publications

Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection.

Zec Kristina K Thiebes Stephanie S Bottek Jenny J Siemes Devon D Spangenberg Philippa P Trieu Duc Viet DV Kirstein Nils N Subramaniam Nirojah N Christ Robin R Klein Diana D Jendrossek Verena V Loose Maria M Wagenlehner Florian F Jablonska Jadwiga J Bracht Thilo T Sitek Barbara B Budeus Bettina B Klein-Hitpass Ludger L Theegarten Dirk D Shevchuk Olga O Engel Daniel R DR

Frontiers in immunology 20230918

<h4>Introduction</h4><i>Streptococcus pneumoniae</i> is one of the main causes of community-acquired infections in the lung alveoli in children and the elderly. Alveolar macrophages (AM) patrol alveoli in homeostasis and under infectious conditions. However, the molecular adaptations of AM upon infections with <i>Streptococcus pneumoniae</i> are incompletely resolved.<h4>Methods</h4>We used a comparative transcriptomic and proteomic approach to provide novel insights into the cellular mechanism ...[more]

PMID: 37790937

Similar Datasets

Project description:Vaccination reduces morbidity and mortality from pneumonia but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute phase response and lung gene expression profiles in mice inoculated intranasally with virulent gram-positive Streptococcus pneumoniae serotype (ST) 3, with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3), or co-immunization with PPS3 and with a low dose of lipopolysaccharide (LPS). Pneumonia severity was assessed in the acute phase, 5, 12, 24 and 48 h post-inoculation (p.i.) and the resolution phase of 7 days p.i. Primary PPS3 specific antibody production was upregulated and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3 + LPS decreased bacterial recovery the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole lung RNA revealed significant changes in the acute phase protein serum amyloid A (SAA) between noninfected and infected mice, which were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum, but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as co-immunization with PPS3 + LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression in the lungs, and acute phase proteins in the lungs, liver and serum. Each lung RNA sample represented an individual mouse, creating biological repeats for each treatment. In-vivo treatments were as follows: non-infected lung (vehicle-immunized) control (n=5), infected lung (vehicle-immunized) control at 48 hr post-inoculation (n=5), PPS3 and LPS co-immunized lung at 48 hr post-inoculation (n=4) and PPS3 and LPS co-immunized lung at 7 days post-inoculation (n=4).

Project description:Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and alter their phenotype in response to local environmental cues. While the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes specifically in lung cancer has not been well studied. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multi-marker flow cytometry we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and express multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor, and selectively express a panel of chemokines genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict good or poor outcome in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and suggest that distinct populations play specific roles in tumor progression. mRNA profiles of macrophage/monocyte cells isolated from murine control or tumor-bearing lung. From naive mice: MacA cells (MacA-N), MacB1 cells (MacB1-N), MacB2 cells (MacB2-N); from 2 week tumor bearing mice: MacA cells (MacA-2wk), MacB2 cells (MacB2-2wk), MacB3 cells (MacB3-3wk); from 3-week tumor bearing mice: MacB2 (MacB2-3wk), MacB3 cells (MacB3-3wk). Each population was analyzed in triplicate (cells were isolated in 3 independent experiments).

Dataset Information

CD11b restricts alveolar macrophage activation during pneumococcal pneumonia and prevents excessive lung inflammation

Publications

Comparative transcriptomic and proteomic signature of lung alveolar macrophages reveals the integrin CD11b as a regulatory hub during pneumococcal pneumonia infection.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure