{"doi":"10.1101/2023.08.16.553579","title":"Iron regulatory proteins 1 and 2 have opposing roles in regulating inflammation in bacterial orchitis","abstract":"Abstract Acute bacterial orchitis (AO) is a prevalent cause of intra-scrotal inflammation, often resulting in sub-or infertility. A frequent cause eliciting AO is uropathogenic Escherichia coli (UPEC), a gram negative pathovar, characterized by the expression of various iron acquisition systems to survive in a low-iron environment. On the host side, iron is tightly regulated by iron regulatory proteins (IRP) 1 and 2 and these factors have been reported to play a role in testicular and immune cell function, however, their precise role remains unclear. Here, we show in a mouse model of UPEC-induced orchitis that the absence of IRP1 results in reduced immune response and testicular damage. Compared to infected wild-type (WT)-mice, testis of UPEC-infected Irp 1 -/- mice showed impaired ERK signalling. Conversely, IRP2 deletion led to a stronger inflammatory response. Notably, differences in immune cell infiltrations were observed among the different genotypes. In contrast to WT and Irp 2 -/- mice, no increase in monocytes and neutrophils was detected in testis of Irp 1 -/- mice upon UPEC-infection. Interestingly, in Irp 1 -/- UPEC-infected testis, we observed an increase in a subpopulation of macrophages (F4/80+ CD206+) associated with anti-inflammatory and wound-healing activities compared to WT. These findings suggest that IRP1 deletion may protect against UPEC-induced inflammation by modulating ERK signalling and dampening the immune response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":410547,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9638,"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":1190510,"name":"Aileen Harrer","orcid":"0009-0004-0247-8902","position":1,"is_corresponding":false},{"id":1190870,"name":"B. Azouly","orcid":null,"position":2,"is_corresponding":false},{"id":1174586,"name":"Noga Guttmann‐Raviv","orcid":null,"position":3,"is_corresponding":false},{"id":1190511,"name":"Sudhanshu Bhushan","orcid":"0000-0002-9088-8108","position":4,"is_corresponding":false},{"id":1190512,"name":"Andreas Meinhardt","orcid":"0000-0003-3711-2746","position":5,"is_corresponding":false},{"id":1174339,"name":"Esther G. Meyron‐Holtz","orcid":"0000-0003-4569-7975","position":6,"is_corresponding":false},{"id":1174335,"name":"Niraj Ghatpande","orcid":"0000-0001-8072-1083","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T01:21:35.071397Z","pmid":null,"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":[]}