Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis

Author:

Houlder E. L.ORCID,Costain A. H.,Nambuya I.,Brown S. L.,Koopman J. P. R.ORCID,Langenberg M. C. C.,Janse J. J.,Hoogerwerf M. A.,Ridley A. J. L.,Forde-Thomas J. E.,Colombo S. A. P.,Winkel B. M. F.,Galdon A. A.,Hoffmann K. F.ORCID,Cook P. C.,Roestenberg M.ORCID,Mpairwe H.,MacDonald A. S.ORCID

Abstract

AbstractSchistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.

Funder

RCUK | Biotechnology and Biological Sciences Research Council

GCRF IAA MCCIR Core funding

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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