# How Does Biological Sex Impact Mucosal Bacterial Infection? Mucosal Defenses and Bacterial Detection

**Authors:** Laura Ramirez Finn, Molly A. Ingersoll

PMC · DOI: 10.1111/imr.70112 · 2026-02-15

## TL;DR

This paper explores how biological sex influences mucosal defenses and immune responses during bacterial infections, focusing on urinary tract infections.

## Contribution

The study highlights the lack of research on sex differences in mucosal barriers and immune responses during bacterial infections.

## Key findings

- Sex disparities exist in urinary tract infection incidence and immune response.
- There is limited understanding of how biological sex affects bladder mucus in homeostasis and infection.
- Sex steroid hormone signaling may influence innate immunity and bacterial detection differences between sexes.

## Abstract

Urinary tract infections possess substantial sex disparities in the incidence, immune response, and progression of infection. Some of these distinctions may be due to sexual dimorphism in mucosal barriers or sex differences in the initial immune response to infection. Mucosal organs are protected by a mucus barrier, however, there is little knowledge of the impact of biological sex on this layer in homeostasis and infection. Notably, despite the incidence of infection, there is a paucity of even fundamental research on bladder mucus in homeostasis and infectious disease. When bacteria encounter mucosal epithelia, they must bind and potentially invade these surfaces to initiate an infection. Whether differences in mucosal epithelia have an impact on bacterial‐epithelial interactions between the sexes is not known. When bacteria are sensed by the host, they initiate transcription factor activation, which may differ by sex of the host. Finally, sex steroid hormone receptor signaling likely also impacts innate immunity between the sexes, leading to the divergence between the sexes observed in mucosa infection.

## Full-text entities

- **Genes:** Map3k7 (mitogen-activated protein kinase kinase kinase 7) [NCBI Gene 26409] {aka B430101B05, Tak1}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, Mucin [NCBI Gene 100508689], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Muc4 (mucin 4) [NCBI Gene 140474] {aka 4933405I11Rik, Asgp}, Il1 (interleukin 1 complex) [NCBI Gene 111343] {aka Il-1}, DDX3X (DEAD-box helicase 3 X-linked) [NCBI Gene 1654] {aka CAP-Rf, DBX, DDX14, DDX3, HLP2, MRX102}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, CCL3 (C-C motif chemokine ligand 3) [NCBI Gene 6348] {aka G0S19-1, LD78, LD78ALPHA, MIP-1-alpha, MIP1A, SCI}, Myd88 (myeloid differentiation primary response gene 88) [NCBI Gene 17874], Esr2 (estrogen receptor 2 (beta)) [NCBI Gene 13983] {aka ER[b], ERbeta, Estrb}, Fdxr (ferredoxin reductase) [NCBI Gene 14149] {aka AR}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, Nod2 (nucleotide-binding oligomerization domain containing 2) [NCBI Gene 257632] {aka ACUG, BLAU, CD, Card15, F830032C23Rik, IBD1}, MUC4 (mucin 4, cell surface associated) [NCBI Gene 4585] {aka ASGP, HSA276359, MUC-4}, Ticam2 (TIR domain containing adaptor molecule 2) [NCBI Gene 225471] {aka B430113A10, TICAM-2, TRAM, Tirp, Trif}, Gper1 (G protein-coupled estrogen receptor 1) [NCBI Gene 76854] {aka 6330420K13Rik, CMKRL2, Ceprl, FEG-1, GPCR-Br, Gper}, Tlr3 (toll-like receptor 3) [NCBI Gene 142980], Cd14 (CD14 antigen) [NCBI Gene 12475], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Junb (jun B proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16477], Ar (androgen receptor) [NCBI Gene 11835] {aka Tfm}, Tlr7 (toll-like receptor 7) [NCBI Gene 170743], Stat5a (signal transducer and activator of transcription 5A) [NCBI Gene 20850] {aka STAT5}, Ifna (interferon alpha complex region) [NCBI Gene 111654] {aka Ifa, Ifa8}, AGR2 (anterior gradient 2, protein disulphide isomerase family member) [NCBI Gene 10551] {aka AG-2, AG2, GOB-4, HAG-2, HEL-S-116, HPC8}, MUC7 (mucin 7, secreted) [NCBI Gene 4589] {aka MG2}, Tlr11 (toll-like receptor 11) [NCBI Gene 239081] {aka Gm287}, Bcl6 (B cell leukemia/lymphoma 6) [NCBI Gene 12053] {aka Bcl5}, Pxn (paxillin) [NCBI Gene 19303] {aka Pax}, Tirap (toll-interleukin 1 receptor (TIR) domain-containing adaptor protein) [NCBI Gene 117149] {aka C130027E04Rik, Mal, Tlr4ap, Wyatt}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Muc1 (mucin 1, transmembrane) [NCBI Gene 17829] {aka CD227, EMA, Muc-1}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, AR (androgen receptor) [NCBI Gene 367] {aka AIS, AR8, DHTR, HPCX3, HUMARA, HYSP1}, Muc5ac (mucin 5, subtypes A and C, tracheobronchial/gastric) [NCBI Gene 17833] {aka 2210005L13Rik, MGM}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Il1a (interleukin 1 alpha) [NCBI Gene 16175] {aka Il-1a}, MUC5B (mucin 5B, oligomeric mucus/gel-forming) [NCBI Gene 727897] {aka MG1, MUC-5B, MUC5, MUC9}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Cybb (cytochrome b-245, beta polypeptide) [NCBI Gene 13058] {aka CGD91-phox, Cgd, Cyd, Nox2, gp91-1, gp91phox}, FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, JUN (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3725] {aka AP-1, AP1, c-Jun, cJUN, p39}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Irf3 (interferon regulatory factor 3) [NCBI Gene 54131] {aka C920001K05Rik, IRF-3}, MUC17 (mucin 17, cell surface associated) [NCBI Gene 140453] {aka MUC-17, MUC-3, MUC3}, Cxcl15 (C-X-C motif chemokine ligand 15) [NCBI Gene 20309] {aka Il8, Scyb15, lungkine, weche}, Ikbkg (inhibitor of kappaB kinase gamma) [NCBI Gene 16151] {aka 1110037D23Rik, IKK[g], NEMO}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, Bmal1 (basic helix-loop-helix ARNT like 1) [NCBI Gene 11865] {aka Arnt3, Arntl, BMAL1b, MOP3, bHLHe5, bmal1b'}, Muc16 (mucin 16) [NCBI Gene 73732] {aka 1110008I14Rik, Ca125, Gm1480, Gm21044}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Cd1d1 (CD1d1 antigen) [NCBI Gene 12479] {aka CD1.1, Cd1a, Cd1d, Ly-38}
- **Diseases:** systemic lupus erythematosus (MESH:D008180), genetic disease (MESH:D030342), Salmonella Infection (MESH:D012480), acute cystitis (MESH:D000208), pyelonephritis (MESH:D011704), chronic obstructive pulmonary disease (MESH:D029424), myocarditis (MESH:D009205), stroke (MESH:D020521), pneumonia (MESH:D011014), autoimmune diseases (MESH:D001327), gastric cancer (MESH:D013274), cystic fibrosis (MESH:D003550), dominant (MESH:C566739), hepatitis B (MESH:D006509), bacteriuria (MESH:D001437), asthma (MESH:D001249), neuroinflammation (MESH:D000090862), decline in lung function (MESH:D055370), Legionnaire's disease (MESH:D007877), Alzheimer's disease (MESH:D000544), reduced lung function (MESH:D001523), lung diseases (MESH:D008171), cancer (MESH:D009369), H. pylori  infections (MESH:D016481), influenza (MESH:D007251), respiratory diseases (MESH:D012140), bacterial vaginosis (MESH:D016585), gastric ulcers (MESH:D013276), Respiratory Bacterial Infections (MESH:D012141), Inflammatory (MESH:D007249), bladder cancer (MESH:D001749), ulcerative colitis (MESH:D003093), sepsis (MESH:D018805), bacterial prostatitis (MESH:D011472), infectious disease (MESH:D003141), incontinence (MESH:D014549), multiple sclerosis (MESH:D009103), endotoxic shock (MESH:D012772), urinary tract malformation (MESH:D014570), neuronal death (MESH:D009410), Bacterial Gastrointestinal Infections (MESH:D001424), Campylobacter infections (MESH:D002169), inflammatory bowel disease (MESH:D015212), kidney infection (MESH:D007674), Mucosa (MESH:D018442), UPEC (MESH:D004927), UTI (MESH:D014552), Crohn's disease (MESH:D003424), Infection (MESH:D007239), coxsackievirus B3 (OMIM:120050), gastrointestinal diseases (MESH:D005767), colitis (MESH:D003092), hypertension (MESH:D006973), death (MESH:D003643), atherosclerosis (MESH:D050197), gut syndrome (MESH:C536735), nosocomial infections (MESH:D003428), rheumatoid arthritis (MESH:D001172)
- **Chemicals:** ceramides (MESH:D002518), chloride (MESH:D002712), hyaluronic acid (MESH:D006820), pentachlorophenol (MESH:D010416), Progesterone (MESH:D011374), GDP (MESH:D006153), HCl (MESH:D006851), Testosterone (MESH:D013739), water (MESH:D014867), sialic acid (MESH:D019158), Triton X-100 (MESH:D017830), As2O3 (MESH:D000077237), lipoteichoic acid (MESH:C009900), glycans (MESH:D011134), 17-beta-estradiol (MESH:D004958), salts (MESH:D012492), sodium pentosan polysulphate (MESH:D010426), oxygen (MESH:D010100), NH3 (MESH:D000641), chondroitin sulphate (MESH:D002809), mannose (MESH:D008358), short chain fatty acids (MESH:D005232), acetate (MESH:D000085), incomplete Freund's adjuvant (MESH:C114843), heparin (MESH:D006493), LPS (MESH:D008070), lipids (MESH:D008055), CO2 (MESH:D002245), Thioglycolate (MESH:D013864), steroid (MESH:D013256), muramyl dipeptide (MESH:D000119), GAG (MESH:D006025), CFT073 (-)
- **Species:** Salmonella enterica subsp. enterica serovar Typhimurium (no rank) [taxon 90371], Human immunodeficiency virus 1 (no rank) [taxon 11676], Sus scrofa (pig, species) [taxon 9823], Pseudomonadota (proteobacteria, phylum) [taxon 1224], Gardnerella vaginalis (species) [taxon 2702], Equus asinus (African ass, species) [taxon 9793], Escherichia coli O157:H7 (no rank) [taxon 83334], Prevotella (genus) [taxon 838], Escherichia coli UTI89 (strain) [taxon 364106], Mus musculus (house mouse, species) [taxon 10090], Pseudomonas aeruginosa (species) [taxon 287], Escherichia coli (E. coli, species) [taxon 562], Eubacteriales (order) [taxon 186802], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Yersinia pseudotuberculosis (species) [taxon 633], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Homo sapiens (human, species) [taxon 9606], Helicobacter pylori (species) [taxon 210], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteroides (genus) [taxon 816], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395]
- **Mutations:** glutamine residue to glutamic acid
- **Cell lines:** Mz-Ch — Homo sapiens (Human), Chondrosarcoma, Cancer cell line (CVCL_M602), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), 5637 — Homo sapiens (Human), Bladder carcinoma, Cancer cell line (CVCL_0126), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), CFT073 — Homo sapiens (Human), Cystic fibrosis, Transformed cell line (CVCL_9640), AF549 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_U801), C57BL/6 — Mus musculus (Mouse), Transformed cell line (CVCL_C0MU), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), TEU-2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628)

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12906789/full.md

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Source: https://tomesphere.com/paper/PMC12906789