phaidra.vetmeduni.ac.at o:3276 DOI 10.3389/fimmu.2024.1407237 Erythrocytes of the common carp are immune sentinels that sense pathogen molecular patterns, engulf particles and secrete pro-inflammatory cytokines against bacterial infection Red blood cells (RBCs), also known as erythrocytes, are underestimated in their role in the immune system. In mammals, erythrocytes undergo maturation that involves the loss of nuclei, resulting in limited transcription and protein synthesis capabilities. However, the nucleated nature of non-mammalian RBCs is challenging this conventional understanding of RBCs. Notably, in bony fishes, research indicates that RBCs are not only susceptible to pathogen attacks but express immune receptors and effector molecules. However, given the abundance of RBCs and their interaction with every physiological system, we postulate that they act in surveillance as sentinels, rapid responders, and messengers.We performed a series of in vitro experiments with Cyprinus carpio RBCs exposed to Aeromonas hydrophila, as well as in vivo laboratory infections using different concentrations of bacteria.qPCR revealed that RBCs express genes of several inflammatory cytokines. Using cyprinid-specific antibodies, we confirmed that RBCs secreted tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ). In contrast to these indirect immune mechanisms, we observed that RBCs produce reactive oxygen species and, through transmission electron and confocal microscopy, that RBCs can engulf particles. Finally, RBCs expressed and upregulated several putative toll-like receptors, including tlr4 and tlr9, in response to A. hydrophila infection in vivo.Overall, the RBC repertoire of pattern recognition receptors, their secretion of effector molecules, and their swift response make them immune sentinels capable of rapidly detecting and signaling the presence of foreign pathogens. By studying the interaction between a bacterium and erythrocytes, we provide novel insights into how the latter may contribute to overall innate and adaptive immune responses of teleost fishes. eng Animals; Carps Immunology Microbiology; Erythrocytes Immunology Metabolism; Cytokines Metabolism Immunology; Aeromonas Hydrophila Immunology; Gram-Negative Bacterial Infections Immunology; Fish Diseases Immunology Microbiology; Phagocytosis Immunology; Pathogen-Associated Molecular Pattern Molecules Immunology; Immunity, Innate 2024-07-23T08:48:43.399Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Majstorović;Jovana; FN:Jovana Majstorović END:VCARD BEGIN:VCARD VERSION:3.0 N:Holzer;Astrid S.; FN:Astrid S. Holzer X-ORCID:https://orcid.org/0000-0002-4916-3172 END:VCARD BEGIN:VCARD VERSION:3.0 N:Korytář;Tomáš; FN:Tomáš Korytář END:VCARD BEGIN:VCARD VERSION:3.0 N:Chan;Justin T. H.; FN:Justin T. H. Chan END:VCARD BEGIN:VCARD VERSION:3.0 N:Maciuszek;Magdalena; FN:Magdalena Maciuszek END:VCARD BEGIN:VCARD VERSION:3.0 N:Kyslík;Jiří; FN:Jiří Kyslík END:VCARD BEGIN:VCARD VERSION:3.0 N:Klak;Katarzyna; FN:Katarzyna Klak END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 6294692 https://phaidra.vetmeduni.ac.at/o:3276 https://phaidra.vetmeduni.ac.at/api/object/o:3276/thumbnail LOMv1.0 discipline