The Framework for Human Host Immune Responses to Four Types of Parasitic Infections and Relevant Key JAK/STAT Signaling
Authors: Wen Tsung-Han , Tsai Kuo-Wang , Wu Yan-Jun , Liao Min-Tser , Lu Kuo-Cheng , Hu Wan-Chung 
Published: December 2021

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 (IFNγ) 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 (IFNγ)/TGFβ 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 STAT5β, and BCL6 expression. Treg is related to STAT5α, STAT5β, and FOXP3. TH1 immunity is related to STAT1α, STAT4, and T-bet. TH2a immunity is related to STAT6, STAT1α, GATA1, and GATA3. TH2b immunity is related to STAT6, STAT3, GATA2, and GATA3. TH22 immunity is associated with both STAT3α and AHR. THαβ immunity is related to STAT1α, STAT1β, STAT2, STAT3β, and ISGF. TH1-like immunity is related to STAT1α, STAT4, STAT5α, and STAT5β. TH9 immunity is related to STAT6, STAT5α, STAT5β, and PU.1. TH17 immunity is related to STAT3α, STAT5α, STAT5β, and RORG. TH3 immunity is related to STAT1α, STAT1β, STAT2, STAT3β, STAT5α, STAT5β, 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.