Intestinal nematode infection exacerbates experimental visceral leishmaniasis

Classon, Cajsa; Feng, Xiaogang; Eidsmo, Liv; Nylén, Susanne

doi:10.1111/pim.12618

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…Yet, the full spectrum of helminth-induced effects on the immune system is not elucidated. Our findings add to the growing body of literature describing how worms can form our immune system and cause extraintestinal immunosuppression 2 , 6 , 13 , 21 , 28 , 34 and propose new ways by which gut-restricted worms impact the onset of skin immune responses. We show that infection with the intestinal nematode H. polygyrus promote homing to and long-term residence of H. polygyrus -specific T H 2 cells producing IL-4 and IL-13 in the skin.…”

Section: Discussionsupporting

confidence: 54%

“…Intestinal worm infection impacts immune responses to other pathogens, vaccines, autoantigens, allergens and contact sensitisers 2 , 6 , 13 , 28 . These effects have been believed to be due to expansion of T REG 2 , 28 , 29 and/or T H 2 cells 21 , 30 , atrophy of peripheral LNs 6 , 31 or changes in the intestinal microbiota or its metabolome 32 – 34 . Yet, the full spectrum of helminth-induced effects on the immune system is not elucidated.…”

Section: Discussionmentioning

confidence: 99%

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

Classon

Clavero

et al. 2022

Mucosal Immunology

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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 TH2 cells that skewed the skin CD4+ T cell composition towards a higher TH2/TH1 ratio which persisted after worm expulsion. Accumulation of TH2 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 TH2 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.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

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

Classon

Clavero

et al. 2022

Mucosal Immunology

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“…donovani growth in the liver and spleen. Similarly, we recently demonstrated [8] that chronic infection with intestinal nematode Heligmosomoides polygyrus exacerbated secondary L . donovani infection in mice, resulting in higher parasite burdens in liver and spleen compared to worm free mice.…”

Section: Introductionmentioning

confidence: 63%

Meta-taxonomic analysis of prokaryotic and eukaryotic gut flora in stool samples from visceral leishmaniasis cases and endemic controls in Bihar State India

et al. 2019

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Visceral leishmaniasis (VL) caused by Leishmania donovani remains of public health concern in rural India. Those at risk of VL are also at risk of other neglected tropical diseases (NTDs) including soil transmitted helminths. Intestinal helminths are potent regulators of host immune responses sometimes mediated through cross-talk with gut microbiota. We evaluate a meta-taxonomic approach to determine the composition of prokaryotic and eukaryotic gut microflora using amplicon-based sequencing of 16S ribosomal RNA (16S rRNA) and 18S rRNA gene regions. The most abundant bacterial taxa identified in faecal samples from Bihar State India were Prevotella (37.1%), Faecalibacterium (11.3%), Escherichia-Shigella (9.1%), Alloprevotella (4.5%), Bacteroides (4.1%), Ruminococcaceae UCG-002 (1.6%), and Bifidobacterium (1.5%). Eukaryotic taxa identified (excluding plant genera) included Blastocystis (57.9%; Order: Stramenopiles), Dientamoeba (12.1%; Family: Tritrichomonadea), Pentatrichomonas (10.1%; Family: Trichomonodea), Entamoeba (3.5%; Family: Entamoebida), Ascaridida (0.8%; Family: Chromodorea; concordant with Ascaris by microscopy), Rhabditida (0.8%; Family: Chromodorea; concordant with Strongyloides), and Cyclophyllidea (0.2%; Order: Eucestoda; concordant with Hymenolepis). Overall alpha (Shannon’s, Faith’s and Pielou’s indices) and beta (Bray-Curtis dissimilarity statistic; weighted UniFrac distances) diversity of taxa did not differ significantly by age, sex, geographic subdistrict, or VL case (N = 23) versus endemic control (EC; N = 23) status. However, taxon-specific associations occurred: (i) Ruminococcaceae UCG- 014 and Gastranaerophilales_uncultured bacterium were enriched in EC compared to VL cases; (ii) Pentatrichomonas was more abundant in VL cases than in EC, whereas the reverse occurred for Entamoeba. Across the cohort, high Escherichia-Shigella was associated with reduced bacterial diversity, while high Blastocystis was associated with high bacterial diversity and low Escherichia-Shigella. Individuals with high Blastocystis had low Bacteroidaceae and high Clostridiales vadin BB60 whereas the reverse held true for low Blastocystis. This scoping study provides useful baseline data upon which to develop a broader analysis of pathogenic enteric microflora and their influence on gut microbial health and NTDs generally.

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“…Intestinal worm infection impact immune responses to other pathogens, vaccines, autoantigens, allergens and contact sensitisers. 2,6,13,24 These effects have been believed to be due to expansion of TREG 2, 24, 25 and/or TH2 cells, 18,26 atrophy of peripheral LNs 6,27 or changes in the intestinal microbiota or its metabolome. [28][29][30] Yet, the full spectrum of helminth-induced effects on the immune system is not elucidated.…”

Section: Discussionmentioning

confidence: 99%

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

Classon

et al. 2021

Preprint

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Intestinal helminth parasites can alter immune responses to vaccines, other infections, allergens and autoantigens, indicating effects on host immune responses in distal barrier tissues. We herein show that C57BL/6 mice infected with the strictly intestinal nematode Heligmosomoides polygyrus have impaired capacity to initiate skin immune responses and develop skin-resident memory cells to mycobacterial antigens, both during infection and months after deworming therapy. Surprisingly, and in contrast to a previously noted loss of T cells in peripheral lymph nodes, the skin of worm-infected mice harboured higher numbers of CD4+ T cells compared to skin of uninfected controls. H. polygyrus-specific TH2 cells accumulated during infection and remained after worm expulsion. Accumulation of TH2 cells in the skin was associated with increased expression of the skin-homing chemokine receptors CCR4 and CCR10 on CD4+ T cells in blood and mesenteric lymph nodes draining intestinal tissues, indicating gut-to-skin trafficking of cells. 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 mechanism for T cell colonization and worm-mediated immunosuppression in this organ.

show abstract

Intestinal nematode infection exacerbates experimental visceral leishmaniasis

Cited by 8 publications

References 35 publications

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

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

Meta-taxonomic analysis of prokaryotic and eukaryotic gut flora in stool samples from visceral leishmaniasis cases and endemic controls in Bihar State India

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

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