Th2 Immune Responses and Alternatively Activated Macrophages (AAMacs) in Helminth Infection in Aged Mice

Sugawara, Yasuhiro; Azuma, Noritsugu; Onodera, Sachi; Tsunoka, Yuichi; Morimoto, Motoko

doi:10.1292/jvms.10-0269

Cited by 18 publications

(19 citation statements)

References 26 publications

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“…The fibrogenic process in the Th2 response profile is dependent on alternatively activated macrophages (AAMs). These cells act in the process of tissue repair, with the participation of IL-4 and IL-13, and stimulate the activation of the arginase enzyme that is involved in induction of fibrosis in different models with helminths (Wilson et al 2007;Sugawara et al 2011;Benzel et al 2012). Importantly, the fibrosis was more evident in the therapeutically treated AIH mice, where the IL-13 in response to Asc was higher than that in the prophylactic protocol.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

et al. 2014

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Adult worm extract from Ascaris suum (Asc) has immunosuppressive activity and elicits Th2/IL-4/IL-10 response. This study evaluated the prophylactic and therapeutic effect of Asc in a murine model of concanavalin A (ConA)-induced autoimmune hepatitis (AIH). BALB/c mice received ConA, iv, (20 mg/kg), and three groups of animals were formed: (1) AIH, received only ConA; (2) AIH + Asc prophylactic, treated with Asc (1 mg/ml), ip, 30 min before of the AIH; and (3) AIH + Asc therapeutic, treated with Asc 2 h after the AIH. Plasma transaminase and immunoglobulins (measured at 8 and 24 h and 7 days after treatment) and cytokine production (IL-4, IL-10, IL-13, and IFN-γ) by splenocytes upon ConA and Asc stimulus were compared. The livers were weighed and examined histologically. In the AIH group, there was an increase in liver weight, transaminase levels, and total immunoglobulins. These parameters were reduced by 8-24 h and 7 days in the prophylactic group, but in the therapeutic group, only on day 7. The survival rate of mice in the AIH group was 38.5%, compared to 67% in the therapeutic Asc group. The survival rate of the animals with AIH that were prophylactically treated with Asc was 100%. A decrease of cellular infiltration and high levels of IL-4, IL-10, and IL-13 were induced by Asc. An increase of liver fibrosis was also observed, but with less intensity with prophylactic treatment. Thus, the Ascaris components have an inhibitory effect on AIH, with an intense Th2 immune response.

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Section: Discussionmentioning

confidence: 99%

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

et al. 2014

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“…This stage is rigorous for the host because of the violent penetration and migration of flukes. In addition, most activity detections of macrophages focus on the early stage of F. hepatica infection [14,45,46]; thus, little is known about the AAMΦ at 6 weeks post F. hepatica infection, which is the reason why the AAMΦ phenotype in MyD88 deficient mice at this stage needs to be addressed.…”

Section: Discussionmentioning

confidence: 99%

The absence of MyD88 has no effect on the induction of alternatively activated macrophage during Fasciola hepatica infection

et al. 2011

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BackgroundAlternatively activated macrophages (AAMϕ) play important roles in allergies and responses to parasitic infections. However, whether signaling through toll-like receptors (TLRs) plays any role in AAMϕ induction when young Fasciola hepatica penetrates the liver capsule and migrates through the liver tissue is still unclear.ResultsThe data show that the lack of myeloid differentiation factor 88 (MyD88) has no effect on the AAMϕ derived from the bone marrow (BMMϕ) in vitro and does not impair the mRNA expression of arginase-1, resistin-like molecule (RELMα), and Ym1 in BMMϕs. The Th2 cytokine production bias in splenocytes was not significantly altered in F. hepatica-infected mice in the absence of MyD88 in vitro and in the pleural cavity lavage in vivo. In addition, MyD88-deficiency has no effect on the arginase production of the F. hepatica elicited macrophages (Fe Mϕs), production of RELMα and Ym1 proteins and mRNA expression of Ym1 and RELMα of macrophages in the peritoneal cavity 6 weeks post F. hepatica infection.ConclusionsThe absence of MyD88 has no effect on presence of AAMϕ 6 weeks post F. hepatica infection.

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“…Macrophages, which are conventionally activated by a Th1‐type response to microparasites, may also be activated by the Th2 cytokines IL‐4 and IL‐13 . These ‘alternatively activated’ macrophages mediate expulsion of adult parasites by production of the enzyme arginase, associated with intestinal hypercontractility, smooth muscle thickening and tissue repair . Another important feature is the production of antibodies by activated B cells, chiefly the isotypes immunoglobulin (Ig)A, E and G and in GI nematode infection, cytokine‐mediated enhancement of intestinal contractility, epithelial turnover and mucin production, which aids worm expulsion .…”

Section: Immune Defence Against Nematodesmentioning

confidence: 99%

Causes and consequences of intra‐ and inter‐host heterogeneity in defence against nematodes

Hayward

2013

Parasite Immunology

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Despite strong natural and artificial selection for increased resistance to nematode parasites, there is considerable heterogeneity between hosts in human, livestock and wildlife populations, with a minority of hosts carrying the majority of parasites. In addition, levels of defence may vary across the lifespan of individuals due to changes in their physiological state and infection history. Such variation influences nematode transmission dynamics and the evolution of parasite life-history strategies. Therefore, identifying sources of between- and within-individual variation in resistance and predicting their consequences is crucial for understanding the epidemiology of nematode parasitic diseases. In this review, several key sources of variation are identified, using examples from mouse models, immuno-epidemiological studies of human populations and observational and experimental studies of wildlife and livestock. The mutual applicability of approaches used across these study systems is emphasized, with the assertion that the concerted efforts of researchers from a range of disciplines will enable us to better understand the proximate and ultimate causes of variation in defence against nematode parasites. This will facilitate predictions of the epidemiological and evolutionary consequences of this variation, with the potential to improve disease treatment and management.

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Th2 Immune Responses and Alternatively Activated Macrophages (AAMacs) in Helminth Infection in Aged Mice

Cited by 18 publications

References 26 publications

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

Immunomodulation of liver injury by Ascaris suum extract in an experimental model of autoimmune hepatitis

The absence of MyD88 has no effect on the induction of alternatively activated macrophage during Fasciola hepatica infection

Causes and consequences of intra‐ and inter‐host heterogeneity in defence against nematodes

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