Co-Infection of Cattle with<i>Fasciola hepatica</i>and<i>Mycobacterium bovis</i>- Immunological Consequences

Flynn, Robin J.; Mulcahy, Grace; Welsh, Michael; Cassidy, Joseph P.; Corbett, David; Milligan, Caitlin; Andersen, Peter; Strain, Sam; McNair, J.

doi:10.1111/j.1865-1682.2009.01075.x

Cited by 68 publications

(75 citation statements)

References 14 publications

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“…F. hepatica secretes molecules that modulate the host immune response and induce the development of a Th2 response and concomitant inhibition of protective pro-inflammatory responses as the disease progresses to chronicity 12, 13 . This polarisation of the immune responses is sufficiently potent to influence the host’s susceptibility to co-infections with bacterial pathogens 13–19 .…”

Section: Introductionmentioning

confidence: 99%

Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Ruiz-Campillo

Molina-Hernández

Escamilla

et al. 2017

Sci Rep

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Immune signatures of sheep acutely-infected with Fasciola hepatica, an important pathogen of livestock and humans were analysed within the peritoneal compartment to investigate early infection. Within the peritoneum, F. hepatica antibodies coincided with an intense innate and adaptive cellular immune response, with infiltrating leukocytes and a marked eosinophilia (49%). However, while cytokine qPCR analysis revealed IL-10, IL-12, IL-13, IL-23 and TGFβ were elevated, these were not statistically different at 18 days post-infection compared to uninfected animals indicating that the immune response is muted and not yet skewed to a Th2 type response that is associated with chronic disease. Proteomic analysis of the peritoneal fluid identified infection-related proteins, including several structural proteins derived from the liver extracellular matrix, connective tissue and epithelium, and proteins related to the immune system. Periostin and vascular cell adhesion protein 1 (VCAM-1), molecules that mediate leukocyte infiltration and are associated with inflammatory disorders involving marked eosinophilia (e.g. asthma), were particularly elevated in the peritoneum. Immuno-histochemical studies indicated that the source of periostin and VCAM-1 was the inflamed sheep liver tissue. This study has revealed previously unknown aspects of the immunology and pathogenesis associated with acute fascioliasis in the peritoneum and liver.

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Section: Introductionmentioning

confidence: 99%

Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Ruiz-Campillo

Molina-Hernández

Escamilla

et al. 2017

Sci Rep

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“…Fasciola hepatica, a parasitic flatworm also known as the common liver fluke, can suppress protective Th1-driven immunity against bystander infections such as tuberculosis and Bordetella pertussis infection (17)(18)(19). It can also attenuate experimental autoimmune encephalomyelitis (EAE) through the suppression of Th17 and Th1 immune responses (20).…”

Section: Ast Cells Are Associated With Helminth Infection Butmentioning

confidence: 99%

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Vukman

Adams

Metz

et al. 2013

The Journal of Immunology

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The parasitic worm Fasciola hepatica induces strong Th2 and T-regulatory immune responses while simultaneously suppressing Th1-driven immune responses to bystander microbial infections. It also prevents the initiation of Th1-mediated autoimmune disorders in mice through the suppression of Th17 and Th1 immune responses, and this can be mimicked by parasite-derived molecules. We have isolated F. hepatica tegumental coat Ag (FhTeg) and demonstrated its suppressive effect in vivo by directly targeting dendritic cells, impairing their ability to drive Th1 responses. Mast cells are critical in promoting Th1 protective immunity during bacterial infection and in driving Th1-mediated pathological conditions in autoimmune diseases. In this article, we show that FhTeg inhibits the ability of mast cells to drive the Th1 immune response by suppressing cytokine secretion (TNF-α, IL-6, IFN-γ, and IL-10) and ICAM1 expression in mast cells stimulated with LPS or heat-inactivated Bordetella pertussis Ag. These heat-inactivated B. pertussis Ag/LPS–stimulated mast cells fail to promote Th1 immune responses in CD4+ T cells when pretreated with FhTeg, and a role for ICAM1 in this process was demonstrated. FhTeg suppresses the activation of transcription factors in the TLR signaling pathway, which explains the decrease in cytokine production and cell surface marker expression. We demonstrated that FhTeg suppresses MAPK and NF-κB activation and enhances SOCS3 expression, which could explain its negative effect on the TLR pathways. We conclude that FhTeg targets innate immune cells, inhibiting their ability to drive Th1 immune responses.

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“…Flooding might exacerbate environmental contamination of grazing pastures or drinking water with M. bovis and might also reduce badger food sources, forcing them to visit farm feed stores, so increasing contact between badgers and cattle (Garnett et al 2002). Additionally, areas prone to flooding may harbour the helminth Fasciola hepatica (liver fluke), and concurrent infection of cattle with this parasite may reduce the sensitivity of the tuberculin skin test (Flynn et al 2009;Ezenwa et al 2010;Claridge et al 2012).…”

Section: Discussionmentioning

confidence: 99%

Using geographically weighted regression to explore the spatially heterogeneous spread of bovine tuberculosis in England and Wales

Brunton

Alexander

Wint

et al. 2016

Stoch Environ Res Risk Assess

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An understanding of the factors that affect the spread of endemic bovine tuberculosis (bTB) is critical for the development of measures to stop and reverse this spread. Analyses of spatial data need to account for the inherent spatial heterogeneity within the data, or else spatial autocorrelation can lead to an overestimate of the significance of variables. This study used three methods of analysis-least-squares linear regression with a spatial autocorrelation term, geographically weighted regression (GWR) and boosted regression tree (BRT) analysis-to identify the factors that influence the spread of endemic bTB at a local level in England and Wales. The linear regression and GWR methods demonstrated the importance of accounting for spatial differences in risk factors for bTB, and showed some consistency in the identification of certain factors related to flooding, disease history and the presence of multiple genotypes of bTB. This is the first attempt to explore the factors associated with the spread of endemic bTB in England and Wales using GWR. This technique improves on least-squares linear regression approaches by identifying regional differences in the factors associated with bTB spread. However, interpretation of these complex regional differences is difficult and the approach does not lend itself to predictive models which are likely to be of more value to policy makers. Methods such as BRT may be more suited to such a task. Here we have demonstrated that GWR and BRT can produce comparable outputs.

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Co-Infection of Cattle withFasciola hepaticaandMycobacterium bovis- Immunological Consequences

Cited by 68 publications

References 14 publications

Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Immune signatures of pathogenesis in the peritoneal compartment during early infection of sheep with Fasciola hepatica

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

Using geographically weighted regression to explore the spatially heterogeneous spread of bovine tuberculosis in England and Wales

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