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

Abstract

Schistosomiasis 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.

Individually or as a Team—The Immunological Milieu in the Lung Caused by Migrating Single-Sex or Mixed-Sex Larvae of Schistosoma mansoni

“…However, the gene expression data showed significantly higher levels of ifn-γ and tnf-α in single-sex infected groups at 4 dpi. Houlder et al implicated a mixed Th1/Th2 response as a hallmark of pre-patent infection in mice naturally infected with both sexes [37]. Our data indicate an emerging Th2 response at the gene and protein level as early as 16 dpi, while in the male + female group, no polarization is identifiable at this time.…”

Gut microbiota and immune profiling of microbiota-humanised versus wildtype mouse models of hepatointestinal schistosomiasis

“…In the future, in-depth time-course studies of the immune response against schistosome infection in HMA mice, including local responses occurring in the skin and lungs (sites of parasite penetration and migration, respectively), will be necessary to clarify these aspects. For instance, correlation analyses between bacterial taxa abundances and levels of immune mediators produced immediately post-cercarial invasion and during the lung migration phase (i.e., from day 0 to day 21 post-infection [ 94 , 95 ]) may assist the identification of key links between host baseline microbiota composition and immunity to infection.…”

Changes in pro inflammatory and regulatory immune responses during controlled human schistosome infection and the development of clinical symptoms

“…Later in infection, at week 8 responses in individuals who had experienced severe symptoms and not/mildly symptomatic individuals converge, with an increased Th2 response and a muted serum Th1 cytokines. Conventional dogma states that egg production is required for Th2 responses in schistosomiasis( 9, 10, 37 ), however, this has recently been challenged by works demonstrating Th2 responses to immature worms in the first month of infection, prior to egg deposition ( 11, 13, 38 ). Our work furthers these findings, showing continued enhancement of Th2 responses up to week 8 post infection, in a single-sex egg-free system.…”

“…One endemic study, looking at individuals with acute schistosomiasis (4-8 weeks post exposure) has shown enhanced production of Th1 (T helper) cytokines (IL-1, TNFα, IFNγ) when compared to chronic schistosomiasis patients, who have higher levels of the Th2 associated cytokine IL-5 ( 9 ). In murine systems egg-production is the major driver of type-2 immune responses in schistosomiasis ( 10 ), with a mixed type-1/type-2 response present in pre-patent or single-sex S. mansoni infection ( 11–13 ).…”