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Patients with autosomal-dominant hyper-IgE syndrome due to STAT3 deficiency are particularly susceptible to acquiring staphylococcal pneumonia associated with lung tissue destruction. Because macrophages are involved in both pathogen defense and inflammation, we investigated the impact of murine myeloid STAT3 deficiency on the macrophage phenotype in vitro and on pathogen clearance and inflammation during murine staphylococcal pneumonia. Murine bone marrow\u2013derived macrophages (BMDM) from STAT3 LysMCre+ knockout or Cre\u2212 wild-type littermate controls were challenged with S. aureus, LPS, IL-4, or vehicle control in vitro. Pro- and anti-inflammatory responses as well as polarization and activation markers were analyzed. Mice were infected intratracheally with S. aureus, bronchoalveolar lavage and lungs were harvested, and immunohistofluorescence was performed on lung sections. S. aureus infection of STAT3-deficient BMDM led to an increased proinflammatory cytokine release and to enhanced upregulation of costimulatory MHC class II and CD86. Murine myeloid STAT3 deficiency did not affect pathogen clearance in vitro or in vivo. Matrix metalloproteinase 9 was upregulated in Staphylococcus-treated STAT3-deficient BMDM and in lung tissues of STAT3 knockout mice infected with S. aureus. Moreover, the expression of miR-155 was increased. The enhanced inflammatory responses and upregulation of matrix metalloproteinase 9 and miR-155 expression in murine STAT3-deficient as compared with wild-type macrophages during S. aureus infections may contribute to tissue damage as observed in STAT3-deficient patients during staphylococcal pneumonia.<\/jats:p>","DOI":"10.4049\/jimmunol.2300151","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T14:38:02Z","timestamp":1700491082000},"page":"69-80","source":"Crossref","is-referenced-by-count":5,"title":["STAT3 Deficiency Alters the Macrophage Activation Pattern and Enhances Matrix Metalloproteinase 9 Expression during Staphylococcal Pneumonia"],"prefix":"10.1093","volume":"212","author":[{"given":"Susan","family":"Farmand","sequence":"first","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Division of Pediatric Stem Cell Transplantation and Immunology, Clinic of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf , Hamburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vicky","family":"Sender","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Clinical Microbiology, Karolinska University Hospital Solna , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8005-9197","authenticated-orcid":false,"given":"Jens","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Clinical Microbiology, Karolinska University Hospital Solna , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Padryk","family":"Merkl","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Staffan","family":"Normark","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitta","family":"Henriques-Normark","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet , Stockholm ,","place":["Sweden"]},{"name":"Clinical Microbiology, Karolinska University Hospital Solna , Stockholm ,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,11,20]]},"reference":[{"key":"2025020405424359000_r1","doi-asserted-by":"crossref","first-page":"214","DOI":"10.15585\/mmwr.mm6809e1","article-title":"Vital signs: epidemiology and recent trends in methicillin-resistant and in methicillin-susceptible Staphylococcus aureus bloodstream infections \u2014 United States","volume":"68","author":"Kourtis","year":"2019","journal-title":"MMWR Morb. 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