PMID- 34948112 OWN - NLM STAT- MEDLINE DCOM- 20220110 LR - 20220110 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 22 IP - 24 DP - 2021 Dec 10 TI - The Framework for Human Host Immune Responses to Four Types of Parasitic Infections and Relevant Key JAK/STAT Signaling. LID - 10.3390/ijms222413310 [doi] LID - 13310 AB - The human host immune responses to parasitic infections are complex. They can be categorized into four immunological pathways mounted against four types of parasitic infections. For intracellular protozoa, the eradicable host immunological pathway is TH1 immunity involving macrophages (M1), interferon gamma (IFNgamma) CD4 T cells, innate lymphoid cells 1 (NKp44+ ILC1), CD8 T cells (Effector-Memory4, EM4), invariant natural killer T cells 1 (iNKT1) cells, and immunoglobulin G3 (IgG3) B cells. For intracellular protozoa, the tolerable host immunological pathway is TH1-like immunity involving macrophages (M2), interferon gamma (IFNgamma)/TGFbeta CD4 T cells, innate lymphoid cells 1 (NKp44- ILC1), CD8 T cells (EM3), invariant natural killer T 1 (iNKT1) cells, and immunoglobulin A1 (IgA1) B cells. For free-living extracellular protozoa, the eradicable host immunological pathway is TH22 immunity involving neutrophils (N1), interleukin-22 CD4 T cells, innate lymphoid cells 3 (NCR+ ILC3), iNKT17 cells, and IgG2 B cells. For free-living extracellular protozoa, the tolerable host immunological pathway is TH17 immunity involving neutrophils (N2), interleukin-17 CD4 T cells, innate lymphoid cells 3 (NCR- ILC3), iNKT17 cells, and IgA2 B cells. For endoparasites (helminths), the eradicable host immunological pathway is TH2a immunity with inflammatory eosinophils (iEOS), interleukin-5/interleukin-4 CD4 T cells, interleukin-25 induced inflammatory innate lymphoid cells 2 (iILC2), tryptase-positive mast cells (MCt), iNKT2 cells, and IgG4 B cells. For ectoparasites (parasitic insects and arachnids), the eradicable host immunological pathway is TH2b immunity with inflammatory basophils, chymase- and tryptase-positive mast cells (MCct), interleukin-3/interleukin-4 CD4 T cells, interleukin-33 induced nature innate lymphoid cells 2 (nILC2), iNKT2 cells, and immunoglobulin E (IgE) B cells. The tolerable host immunity against ectoparasites and endoparasites is TH9 immunity with regulatory eosinophils, regulatory basophils, interleukin-9 mast cells (MMC9), thymic stromal lymphopoietin induced innate lymphoid cells 2, interleukin-9 CD4 T cells, iNKT2 cells, and IgA2 B cells. In addition, specific transcription factors important for specific immune responses were listed. This JAK/STAT signaling is key to controlling or inducing different immunological pathways. In sum, Tfh is related to STAT5beta, and BCL6 expression. Treg is related to STAT5alpha, STAT5beta, and FOXP3. TH1 immunity is related to STAT1alpha, STAT4, and T-bet. TH2a immunity is related to STAT6, STAT1alpha, GATA1, and GATA3. TH2b immunity is related to STAT6, STAT3, GATA2, and GATA3. TH22 immunity is associated with both STAT3alpha and AHR. THalphabeta immunity is related to STAT1alpha, STAT1beta, STAT2, STAT3beta, and ISGF. TH1-like immunity is related to STAT1alpha, STAT4, STAT5alpha, and STAT5beta. TH9 immunity is related to STAT6, STAT5alpha, STAT5beta, and PU.1. TH17 immunity is related to STAT3alpha, STAT5alpha, STAT5beta, and RORG. TH3 immunity is related to STAT1alpha, STAT1beta, STAT2, STAT3beta, STAT5alpha, STAT5beta, and ISGF. This categorization provides a complete framework of immunological pathways against four types of parasitic infections. This framework as well as relevant JAK/STAT signaling can provide useful knowledge to control allergic hypersensitivities and parasitic infections via development of vaccines or drugs in the near future. FAU - Wen, Tsung-Han AU - Wen TH AD - Department of Anatomical Pathology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan. FAU - Tsai, Kuo-Wang AU - Tsai KW AUID- ORCID: 0000-0002-9028-9834 AD - Department of Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan. FAU - Wu, Yan-Jun AU - Wu YJ AD - Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan City 325, Taiwan. FAU - Liao, Min-Tser AU - Liao MT AD - Department of Pediatrics, Taoyuan Armed Forces General Hospital, Taoyuan City 325, Taiwan. FAU - Lu, Kuo-Cheng AU - Lu KC AUID- ORCID: 0000-0002-7062-8560 AD - Division of Nephrology, Department of Medicine, Fu-Jen Catholic University Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan. FAU - Hu, Wan-Chung AU - Hu WC AUID- ORCID: 0000-0003-1360-1422 AD - Department of Clinical Pathology & Medical Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation No. 289, Jianguo Road, Xindian District, New Taipei City 231, Taiwan. LA - eng GR - TCRD-TPE-110-45/Taipei Tzu Chi Hospital/ PT - Journal Article PT - Review DEP - 20211210 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Cytokines) SB - IM MH - Cytokines/*immunology MH - Humans MH - *Immunity, Innate MH - Leukocytes/*immunology MH - Parasitic Diseases/*immunology PMC - PMC8705408 OTO - NOTNLM OT - JAK/STAT OT - basophils OT - eosinophils OT - helminths OT - immune response OT - mast cells OT - parasitic infection OT - parasitic insects OT - protozoa COIS- The authors declare that the manuscript was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/12/25 06:00 MHDA- 2022/01/11 06:00 PMCR- 2021/12/10 CRDT- 2021/12/24 01:16 PHST- 2021/10/20 00:00 [received] PHST- 2021/12/03 00:00 [revised] PHST- 2021/12/08 00:00 [accepted] PHST- 2021/12/24 01:16 [entrez] PHST- 2021/12/25 06:00 [pubmed] PHST- 2022/01/11 06:00 [medline] PHST- 2021/12/10 00:00 [pmc-release] AID - ijms222413310 [pii] AID - ijms-22-13310 [pii] AID - 10.3390/ijms222413310 [doi] PST - epublish SO - Int J Mol Sci. 2021 Dec 10;22(24):13310. doi: 10.3390/ijms222413310.