Intestinal helminth infection transforms the CD4+ T cell composition of the skin

• Published in: Mucosal immunology Vol. 15; no. 2; pp. 257 - 267
• Main Authors: Classon, Cajsa H., Li, Muzhen, Clavero, Ada Lerma, Ma, Junjie, Feng, Xiaogang, Tibbitt, Christopher A., Stark, Julian M., Cardoso, Rebeca, Ringqvist, Emma, Boon, Louis, Villablanca, Eduardo J., Rothfuchs, Antonio Gigliotti, Eidsmo, Liv, Coquet, Jonathan M., Nylén, Susanne
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2022; Elsevier Limited
• Subjects: Allergens; Allergology; Animals; Antibodies; Antigens; Autoantigens; Biomedical and Life Sciences; Biomedicine; CD4 antigen; Chemokine receptors; FTY720; Gastroenterology; Helper cells; Immunological memory; Immunology; Immunosuppression; Infections; Intestinal Diseases, Parasitic; Intestine; Long-term effects; Lymph nodes; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Memory cells; Mice; Mice, Inbred C57BL; Nematospiroides dubius; Skin; Strongylida Infections; Th2 Cells; γ-Interferon
• ISSN: 1933-0219; 1935-3456; 1935-3456
• DOI: 10.1038/s41385-021-00473-9

Intestinal helminth parasites can alter immune responses to vaccines, other infections, allergens and autoantigens, implying effects on host immune responses in distal barrier tissues. We herein show that the skin of C57BL/6 mice infected with the strictly intestinal nematode Heligmosomoides polygyrus contain higher numbers of CD4 +  T cells compared to the skin of uninfected controls. Accumulated CD4 +  T cells were H. polygyrus- specific T H 2 cells that skewed the skin CD4 +  T cell composition towards a higher T H 2/T H 1 ratio which persisted after worm expulsion. Accumulation of T H 2 cells in the skin was associated with increased expression of the skin-homing chemokine receptors CCR4 and CCR10 on CD4 +  T cells in the blood and mesenteric lymph nodes draining the infected intestine and was abolished by FTY720 treatment during infection, indicating gut-to-skin trafficking of cells. Remarkably, skin T H 2 accumulation was associated with impaired capacity to initiate IFN- γ recall responses and develop skin-resident memory cells to mycobacterial antigens, both during infection and months after deworming therapy. In conclusion, we show that infection by a strictly intestinal helminth has long-term effects on immune cell composition and local immune responses to unrelated antigens in the skin, revealing a novel process for T cell colonisation and worm-mediated immunosuppression in this organ.