Maternal helminth infections and the shaping of offspring immunity

Dewals, Benjamin G; Layland, Laura E.; Costa, Clarissa Prazeres da; Horsnell, William G. C.

doi:10.1111/pim.12599

Cited by 9 publications

(10 citation statements)

References 109 publications

(125 reference statements)

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“…Moreover, the remodelled DNA-methylation signatures and defective TB-specific Th1 responses were maintained for up to at least 6 months following successful deworming of S. haematobium 102 . Furthermore, intriguingly, emerging evidence suggests that the offspring of chronically-infected mothers display epigenetically rewired immune responses that potentially shape their reactions to other pathogens (bacterial and viral infections) and vaccines 103, 104 . In conclusion therefore, understanding these interactive epigenetic networks has important implications not only for how to develop strategies to counter the rise in prevalence of chronic inflammatory (allergic and autoimmune) conditions, increasingly associated with eradication of helminths, but also to combat pathogens in a co-infection setting.…”

Section: Discussionmentioning

confidence: 99%

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

Corbet

Pineda

Yang

et al. 2020

Preprint

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The parasitic worm product, ES-62 protects against collagen-induced arthritis, a mouse model of rheumatoid arthritis (RA) by suppressing the synovial fibroblast (SF) responses perpetuating inflammation and driving joint destruction. Such SF responses are shaped during disease progression by the inflammatory microenvironment of the joint that promotes remodelling of their epigenetic landscape, inducing an “aggressive” pathogenic SF phenotype. Critically, exposure to ES-62 in vivo induces a stably imprinted “safe” phenotype that exhibits responses more typical of healthy SFs. Surprisingly however, DNA methylome analysis reveals that rather than simply preventing the pathogenic rewiring of SFs, ES-62 induces further epigenetic remodelling, including targeting genes associated with ciliogenesis and differentiation, to program a distinct “protective” phenotype. Such unique behaviour signposts potential DNA methylation signatures predictive of pathogenesis and its resolution and hence, candidate mechanisms by which novel therapeutic interventions could prevent SFs from perpetuating joint inflammation and destruction in RA.

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Section: Discussionmentioning

confidence: 99%

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

Corbet

Pineda

Yang

et al. 2020

Preprint

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“…Epidemiological and experimental evidence indicates that maternal immune transfer via nursing may also provide long-lasting pathogen-specific protection from infection, despite the short half-life of substances transferred via breast milk ( 7 , 8 ). However, the mechanisms underlying any such long-term protection are not well defined, and the contribution from incorporation and maintenance of maternal components by offspring has hitherto been relatively unaddressed ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

“…Helminth infections are an important cause of infection and disease and leave profound immunological footprints on a host ( 9 , 10 ). These infections are extremely common and have important effects on multiple components of host immunity.…”

Section: Introductionmentioning

confidence: 99%

“…The mechanisms underlying these maternally associated effects in offspring are, however, not well defined. As helminth exposure is a huge global coordinator of our immunological footprint, understanding this influence in the context of the maternal-offspring immunological relationship is important ( 9 ). This transgenerational immunological relationship is pivotal for our understanding of how early-life events influence lifelong ability to control disease.…”

Section: Introductionmentioning

confidence: 99%

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Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring

et al. 2019

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Maternal immune transfer is the most significant source of protection from early-life infection, but whether maternal transfer of immunity by nursing permanently alters offspring immunity is poorly understood. Here, we identify maternal immune imprinting of offspring nursed by mothers who had a pre-conception helminth infection. Nursing of pups by helminth-exposed mothers transferred protective cellular immunity to these offspring against helminth infection. Enhanced control of infection was not dependent on maternal antibody. Protection associated with systemic development of protective type 2 immunity in T helper 2 (TH2) impaired IL-4Rα−/− offspring. This maternally acquired immunity was maintained into maturity and required transfer (via nursing) to the offspring of maternally derived TH2-competent CD4 T cells. Our data therefore reveal that maternal exposure to a globally prevalent source of infection before pregnancy provides long-term nursing-acquired immune benefits to offspring mediated by maternally derived pathogen-experienced lymphocytes.

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“…Finally, our review addressing maternal helminth exposure addresses further how maternal parasitic infections can result in an immunological footprint in the offspring which has long‐term ramifications for subsequent helminth and bystander exposures. We also summarize the main mechanisms involved in shaping the offspring's immune system after maternal infection with helminths and highlight the importance of antibody transfer, antigen exposure, maternal cell uptake, microchimerism and epigenetic effects during gestation and/or nursing.…”

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confidence: 99%

Parasitic infections and maternal immunity

Horsnell

Dewals

2019

Parasite Immunology

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Our parents' health is well appreciated as being able to exert transgenerational influences on our health and is a central target in achieving millennium goals for reducing infant mortality. 1 Indeed, components of this interaction are now being specifically targeted in the clinic. The efficacy of maternal vaccination in protecting nursing children against potentially life-threatening infections such as respiratory syncytial virus (RSV) and group B streptococcal (GBS) infections 2 is one such example.Transgenerational effects are not limited to protection from infection but also extend to influencing our susceptibility to a range of non-communicable diseases (NCDs). Publications in 1970s and 1980s by Forsdahl 3 and Barker 4 have been central to our appreciation of the significance of trans-generational influences on NCDs.These publications promoted observations that poor living conditions in childhood and adolescence were an important risk factor for heart disease that this increased risk was likely to have foetal origins and the ramifications of these observations were likely to be wide reaching. This work led to the Forsdahl/Barker Developmental Origins of Health and Disease (DOHaD) hypothesis, which is now supported by epidemiological studies in a range of disease settings addressing infant and adult mortality. 5 These have well documented that intrauterine and early life are important windows of influence on our health later in life. This work has had an enormous impact on health policy and healthcare programmes for mothers and children.Our understanding of these transgenerational effects on health is now extending rapidly. We know that exposures before conception influence health and disease and recent studies suggest that not only mothers' but also fathers' health, behaviour and environment influence the health of future generations. 6,7 Transgenerational effects on health can also be surprisingly profound. Effects can be independent of dosing and instead related to the timing of exposure. Relatively benign exposures to an adult may have significant effects if occurring at more susceptible time windows, such as in adolescence or in utero. For example, a parent's diet can predispose to pancreatic beta-cell dysfunction and subsequent risk of insulin intolerance in offspring. 8 The review articles in this special issue of Parasite Immunology discuss the influence of parasitic infections on maternal transfer of immunity and the consequences of this for both offspring and the mother. Certain parasitic infections are established as having extremely significant pathology which is intricately linked to maternal infection. Toxoplasmosis was (prior to the HIV-AIDs epidemic) primarily associated with the risk of congenital exposure resulting in acute neurological pathology in the child. In addition to this welldocumented effect of T. gondii infection, the review by Borges et al 9 introduces the concept that Toxoplasma gondii may also influence the success of coitus, an effect which has also been suggested to apply to ...

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Maternal helminth infections and the shaping of offspring immunity

Cited by 9 publications

References 109 publications

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

ES-62 suppression of arthritis reflects epigenetic rewiring of synovial fibroblasts to a joint-protective phenotype

Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring

Parasitic infections and maternal immunity

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