{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:37:14Z","timestamp":1787027834523,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["BR 3880\/4-1"],"award-info":[{"award-number":["BR 3880\/4-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["PA 1933\/7-1"],"award-info":[{"award-number":["PA 1933\/7-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["PA 1933\/2-3"],"award-info":[{"award-number":["PA 1933\/2-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The mRNA-binding protein KSRP (KH-type splicing regulatory protein) is known to modulate immune cell functions post-transcriptionally, e.g., by reducing the mRNA stability of cytokines. It is known that KSRP binds the AU-rich motifs (ARE) that are often located in the 3\u2032-untranslated part of mRNA species, encoding dynamically regulated proteins as, for example, cytokines. Innate myeloid immune cells, such as polymorphonuclear neutrophils (PMNs) and macrophages (MACs), eliminate pathogens by multiple mechanisms, including phagocytosis and the secretion of chemo- and cytokines. Here, we investigated the role of KSRP in the phenotype and functions of both innate immune cell types in the mouse model of invasive pulmonary aspergillosis (IPA). Here, KSRP\u2212\/\u2212 mice showed lower levels of Aspergillus fumigatus conidia (AFC) and an increase in the frequencies of PMNs and MACs in the lungs. Our results showed that PMNs and MACs from KSRP\u2212\/\u2212 mice exhibited an enhanced phagocytic uptake of AFC, accompanied by increased ROS production in PMNs upon stimulation. A comparison of RNA sequencing data revealed that 64 genes related to inflammatory and immune responses were shared between PMNs and MACs. The majority of genes upregulated in PMNs were involved in metabolic processes, cell cycles, and DNA repair. Similarly, KSRP-deficient PMNs displayed reduced levels of apoptosis. In conclusion, our results indicate that KSRP serves as a critical negative regulator of PMN and MAC anti-pathogen activity.<\/jats:p>","DOI":"10.3390\/cells13242040","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T08:40:10Z","timestamp":1733820010000},"page":"2040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["KSRP Deficiency Attenuates the Course of Pulmonary Aspergillosis and Is Associated with the Elevated Pathogen-Killing Activity of Innate Myeloid Immune Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Vanessa","family":"Bolduan","sequence":"first","affiliation":[{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim-Alicia","family":"Palzer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Ries","sequence":"additional","affiliation":[{"name":"Department of Hematology and Medical Oncology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Busch","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3969-0056","authenticated-orcid":false,"given":"Andrea","family":"Pautz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Bros","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.bbagrm.2012.11.003","article-title":"Functional and molecular insights into KSRP function in mRNA decay","volume":"1829","author":"Briata","year":"2013","journal-title":"Biochim. 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