# Transcriptomic and proteomic profiling of pulmonary mucormycosis reveals a failed activation of host immune response **Authors:** Jinjin Zhong, Xiaomin Cai, Yuchen Cai, Tingting Zhao, Die Hu, Chao Sun, Yueyan Ni, Yu Gu, Xin Su PMC · DOI: 10.3389/fimmu.2026.1732782 · Frontiers in Immunology · 2026-02-13 ## TL;DR This study explores how the immune system responds to a deadly fungal lung infection using gene and protein analysis, revealing a weak immune response that could inform better treatments. ## Contribution The first combined transcriptomic and proteomic analysis of immune responses in pulmonary mucormycosis. ## Key findings - Transcriptomic analysis showed up-regulated genes related to immune defense, iron metabolism, and cytokines. - Proteomic profiling revealed limited immune protein activation and suppressed host defense pathways. - Findings suggest compromised immune function at infection sites, pointing to potential treatment strategies. ## Abstract Mucormycosis is one of the most life-threatening fungal infections with delayed diagnosis and limited antifungal treatments. The transcriptome and proteome of pulmonary mucormycosis have not been fully investigated. We obtained lung tissues and paired controls from five pulmonary mucormycosis patients and utilized transcriptomic and proteomic approaches to explore host immune response during pulmonary mucormycosis. Our transcriptomic analysis found a number of up-regulated genes and pathways associated with immune defense. These genes were related to iron metabolism, pattern recognition receptors (PRRs), cytokines, chemokines et al., which enriched in pathways involved in both innate and adaptive immunity. However, proteomic profiling revealed limited upregulation of immune-related proteins and global suppression of pathways associated with host defense, especially those related to cell junction and cytoskeletal dynamics, indicating a failed activation of host immune response. Given the findings of compromised immune function at infection sites, enhancing adjuvant immunotherapy and intensifying localized antifungal treatments may be beneficial for this refractory infection. Our study firstly investigated the immune landscape in pulmonary mucormycosis through combined transcriptomic and proteomic profiling, which could provide novel mechanistic insights for the prevention and treatment of pulmonary mucormycosis. ## Full-text entities - **Genes:** SPATA2 (spermatogenesis associated 2) [NCBI Gene 9825] {aka PD1, PPP1R145, tamo}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, CCR7 (C-C motif chemokine receptor 7) [NCBI Gene 1236] {aka BLR2, CC-CKR-7, CCR-7, CD197, CDw197, CMKBR7}, ARHGEF1 (Rho guanine nucleotide exchange factor 1) [NCBI Gene 9138] {aka GEF1, IMD62, LBCL2, LSC, P115-RHOGEF, SUB1.5}, TLR2 (toll like receptor 2) [NCBI Gene 7097] {aka CD282, TIL4}, TNFRSF13C (TNF receptor superfamily member 13C) [NCBI Gene 115650] {aka BAFF-R, BAFFR, BROMIX, CD268, CVID4, prolixin}, CCL19 (C-C motif chemokine ligand 19) [NCBI Gene 6363] {aka CKb11, ELC, MIP-3b, MIP3B, SCYA19}, TNFRSF17 (TNF receptor superfamily member 17) [NCBI Gene 608] {aka BCM, BCMA, CD269, TNFRSF13A}, MSC (musculin) [NCBI Gene 9242] {aka ABF-1, ABF1, MYOR, bHLHa22}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, FCRL5 (Fc receptor like 5) [NCBI Gene 83416] {aka BXMAS1, CD307, CD307e, FCRH5, IRTA2, PRO820}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}, LTF (lactotransferrin) [NCBI Gene 4057] {aka GIG12, HEL110, HLF2, LF}, SIRPG (signal regulatory protein gamma) [NCBI Gene 55423] {aka CD172g, SIRP-B2, SIRPB2, SIRPgamma, bA77C3.1}, JCHAIN (joining chain of multimeric IgA and IgM) [NCBI Gene 3512] {aka IGCJ, IGJ, JCH}, BPIFB1 (BPI fold containing family B member 1) [NCBI Gene 92747] {aka C20orf114, LPLUNC1}, CXCL13 (C-X-C motif chemokine ligand 13) [NCBI Gene 10563] {aka ANGIE, ANGIE2, BCA-1, BCA1, BLC, BLR1L}, IGDCC4 (immunoglobulin superfamily DCC subclass member 4) [NCBI Gene 57722] {aka DDM36, NOPE}, CLEC7A (C-type lectin domain containing 7A) [NCBI Gene 64581] {aka BGR, CANDF4, CD369, CLECSF12, DECTIN1, SCARE2}, FCRLA (Fc receptor like A) [NCBI Gene 84824] {aka FCRL, FCRLM1, FCRLX, FCRLb, FCRLc1, FCRLc2}, LAX1 (lymphocyte transmembrane adaptor 1) [NCBI Gene 54900] {aka LAX}, HSH2D (hematopoietic SH2 domain containing) [NCBI Gene 84941] {aka ALX, HSH2}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, AIM2 (absent in melanoma 2) [NCBI Gene 9447] {aka PYHIN4}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, IFITM10 (interferon induced transmembrane protein 10) [NCBI Gene 402778] {aka DSPA3}, TNFRSF9 (TNF receptor superfamily member 9) [NCBI Gene 3604] {aka 4-1BB, CD137, CDw137, ILA, IMD109}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, IRF4 (interferon regulatory factor 4) [NCBI Gene 3662] {aka IMD131, LSIRF, MUM1, NF-EM5, SHEP8}, RAP1A (RAP1A, member of RAS oncogene family) [NCBI Gene 5906] {aka C21KG, G-22K, KREV-1, KREV1, RAP1, SMGP21}, SLAMF6 (SLAM family member 6) [NCBI Gene 114836] {aka CD352, KALI, KALIb, Ly108, NTB-A, NTBA}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, FCRL4 (Fc receptor like 4) [NCBI Gene 83417] {aka CD307d, FCRH4, IGFP2, IRTA1}, HP (haptoglobin) [NCBI Gene 3240] {aka HP2ALPHA2, HPA1S}, CD72 (CD72 molecule) [NCBI Gene 971] {aka CD72b, LYB2}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, ATP6AP2 (ATPase H+ transporting accessory protein 2) [NCBI Gene 10159] {aka (P)RR, APT6M8-9, ATP6IP2, ATP6M8-9, CDG2R, ELDF10}, BLK (BLK proto-oncogene, Src family tyrosine kinase) [NCBI Gene 640] {aka MODY11}, RUFY4 (RUN and FYVE domain containing 4) [NCBI Gene 285180] {aka ZFYVE31}, F3 (coagulation factor III, tissue factor) [NCBI Gene 2152] {aka CD142, TF, TFA}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, LY9 (lymphocyte antigen 9) [NCBI Gene 4063] {aka CD229, SLAMF3, hly9, mLY9}, DCLK3 (doublecortin like kinase 3) [NCBI Gene 85443] {aka CLR, DCAMKL3, DCDC3C, DCK3}, CTLA4 (cytotoxic T-lymphocyte associated protein 4) [NCBI Gene 1493] {aka ALPS5, CD, CD152, CELIAC3, CTLA-4, GRD4}, IFRD1 (interferon related developmental regulator 1) [NCBI Gene 3475] {aka PC4, TIS7}, VPREB3 (V-set pre-B cell surrogate light chain 3) [NCBI Gene 29802] {aka 8HS20, N27C7-2}, NCF4 (neutrophil cytosolic factor 4) [NCBI Gene 4689] {aka CGD3, NCF, P40PHOX, SH3PXD4}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, IL17REL (interleukin 17 receptor E like) [NCBI Gene 400935], IGLL5 (immunoglobulin lambda like polypeptide 5) [NCBI Gene 100423062] {aka IGLV, VL-MAR}, CD28 (CD28 molecule) [NCBI Gene 940] {aka IMD123, Tp44}, CSF2 (colony stimulating factor 2) [NCBI Gene 1437] {aka CSF, GMCSF}, FCRL2 (Fc receptor like 2) [NCBI Gene 79368] {aka CD307b, FCRH2, IFGP4, IRTA4, SPAP1, SPAP1A}, CD27 (CD27 molecule) [NCBI Gene 939] {aka S152, S152. LPFS2, T14, TNFRSF7, Tp55}, CD19 (CD19 molecule) [NCBI Gene 930] {aka B4, CVID3}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, MUC5AC (mucin 5AC, oligomeric mucus/gel-forming) [NCBI Gene 4586] {aka MUC5, TBM, leB, mucin}, VMP1 (vacuole membrane protein 1) [NCBI Gene 81671] {aka EPG3, TANGO5, TMEM49} - **Diseases:** Hyperglycemia (MESH:D006943), Pneumocystis (MESH:D011020), In Melanoma 2 (MESH:D008545), iron overload (MESH:D019190), inflammatory (MESH:D007249), trauma (MESH:D014947), cancer (MESH:D009369), opportunistic infection (MESH:D009894), lung (MESH:D008171), Diabetes (MESH:D003920), lung injury (MESH:D055370), Malassezia folliculitis (MESH:D005499), Paraccocidium brasiliensis infection (MESH:D010229), primary immunodeficiency (MESH:D000081207), metabolic dysregulation (MESH:D021081), Cryptococcus neoformans infections (MESH:D003453), mucor infection (MESH:C000656945), hypoxia (MESH:D000860), iron (MESH:D000090463), rheumatoid arthritis (MESH:D001172), malarial anemia (MESH:D000740), neutropenia (MESH:D009503), malnourishment (MESH:D044342), Lacazia loboi infection (MESH:D060368), CAM (MESH:D000086382), Infected (MESH:D007239), allergic bronchopulmonary aspergillosis (MESH:D001229), Mucormycosis (MESH:D009091), fusarium keratitis (MESH:D060585), autoimmune thyroid disease (MESH:D013967), DKA (MESH:D016883), type I diabetes mellitus (MESH:D003922), rhino-orbital (MESH:D009916), Candida infection (MESH:D002177), T-cell leukemia virus 1 infection (MESH:D015458), ketoacidosis (MESH:D007662), fungal (MESH:D009181), Aspergillus (MESH:D001228), invasive fungal infection (MESH:D000072742), infectious diseases (MESH:D003141) - **Chemicals:** FA (MESH:C030544), AGE (MESH:D017127), Trizol (MESH:C411644), Iron (MESH:D007501), posaconazole (MESH:C101425), SDS (MESH:D012967), Amphotericin B. (MESH:D000666), isavuconazole (MESH:C508735), BCA (MESH:C047117), agarose (MESH:D012685), ROS (MESH:D017382), polyA (MESH:D011061), beta-glucans (MESH:D047071) - **Species:** Candida albicans (species) [taxon 5476], Aspergillus fumigatus (species) [taxon 746128], Rhizopus arrhizus (species) [taxon 64495], Mus musculus (house mouse, species) [taxon 10090], Mucor (genus) [taxon 4830], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Cunninghamella (genus) [taxon 4852], Apophysomyces (genus) [taxon 90268], Histoplasma capsulatum (species) [taxon 5037], Rhizomucor (genus) [taxon 4838], Lichtheimia (genus) [taxon 688353], Blastomyces dermatitidis (species) [taxon 5039], Rhizopus (genus) [taxon 4842], Actinomucor (genus) [taxon 64644], Syncephalastrum (genus) [taxon 13705], Danio rerio (leopard danio, species) [taxon 7955], Homo sapiens (human, species) [taxon 9606], tomato spotted wilt virus [taxon 1933298], Candida [taxon 1535326], Cokeromyces (genus) [taxon 90254], Drosophila melanogaster (fruit fly, species) [taxon 7227] ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12945811/full.md ## Figures 4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12945811/full.md ## References 129 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945811/full.md --- Source: https://tomesphere.com/paper/PMC12945811