Immune modulation by helminths and the impact on the development of type 2 diabetes
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Abstract:
The main objective of this
thesis is to improve the understanding of the role of helminth infections in
the development of insulin resistance, hence type 2 diabetes, and to gain
insight into the immunological mechanisms underlying this possible interaction.
To this end, we initiated a large scale cluster randomized controlled trial,
assessing the effect of anthelmintic treatment on insulin resistance and other
metabolic, as well as immunological parameters, in a rural area of Indonesia.
Deworming significantly reduced the prevalence of helminths, as well as
infection intensity. Although treatment did not lead to an increase of
whole-body insulin resistance at the community level, a significant increase in
insulin resistance was observed among helminth-infected subjects. Furthermore,
by comparing immune cells of helminth-infected Indonesians before and after
treatment, we gained insight into the specific cell populations that
participate in the type 2 and regulatory networks, and show that treatment
affects specific cell subsets in these networks. Altogether, the studies
described in this thesis show that helminth infections in humans, as well as
the administration of helminth molecules in obese mice, have a beneficial effect
on the insulin sensitivity, and have shed light on the immunomodulatory effects
of helminths.Keywords:
Deworming
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Infection with intestinal helminths may stimulate dysfunctional immune responses in human immunodeficiency virus (HIV)-infected persons. Studies have yielded conflicting results regarding the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA.Methods. We conducted a prospective study of 54 HIV-1- and helminth-coinfected and 57 HIV-1-infected, helminth-uninfected asymptomatic adults living in Lusaka, Zambia, to assess the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA.Median baseline viral load was 0.33 log(10) copies/mL lower in the helminth-infected group than in the uninfected group. Mean viral load between pretreatment and posttreatment visits increased in the helminth-infected (mean, 4.23 vs. 4.29 log(10) copies/mL; P=.6) and helminth-uninfected (mean, 4.39 vs. 4.52 log(10) copies/mL; P=.2) groups. Helminth-infected participants with high pretreatment viral loads had a mean 0.25-log(10) copies/mL decrease after treatment (P=.3), and helminth-uninfected participants had a mean 0.02-log(10) copies/mL decrease (P=.8).We did not find an overall association between treatment of intestinal helminth infections and reduction in viral load in coinfected adults. Future studies may need to focus on adults with intense helminth infections who live in rural areas or on adults or children who harbor higher helminth burdens and plasma concentrations of HIV-1 RNA.
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The interaction between diabetes and major world infections like TB is a major public health concern because of rapidly rising levels of diabetes. The dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a major global public health problem. Diabetes mellitus is a major risk factor for the development of active and latent tuberculosis. Immune mechanisms contributing to the increased susceptibility of diabetic patients to TB are due to the defects in bacterial recognition, phagocytic activity, and cellular activation which results in impaired production of chemokines and cytokines. The initiation of adaptive immunity is delayed by impaired antigen-presenting cell (APC) recruitment and function in hyperglycemic host, which results in reduced frequencies of Th1, Th2, and Th17 cells and its secretion of cytokines having a great role in activation of macrophage and inflammatory response of tuberculosis. In addition, impaired immune response and killing of intracellular bacteria potentially increase bacterial load, chronic inflammation, and central necrosis that facilitate bacterial dissemination and miliary tuberculosis. Understanding of the immunological and biochemical basis of TB susceptibility in diabetic patients will tell us the rational development of implementation and therapeutic strategies to alleviate the dual burden of the diseases. Therefore, the aim of this review was focused on the association between diabetes and tuberculosis, focusing on epidemiology, pathogenesis, and immune dysfunction in diabetes mellitus, and its association with susceptibility, severity, and treatment outcome failure to tuberculosis.
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Public Health![Figure][1]
Ascaris lumbricoides is a common parasite of humans.
PHOTO: EYE OF SCIENCE/SCIENCE SOURCE
Rural populations in less developed countries commonly show poor immunogenicity in vaccination programs. Helminth infestations remain common in some rural areas, and cellular immune hyporesponsiveness is a hallmark of chronic helminth infections. Community deworming programs are in general believed to be a good thing to reverse the morbidity that a large worm burden can impose on children. Wammes et al. set up a 2-year clinical trial to systematically test the immunological consequences of deworming in >1000 villagers in Indonesia. After treatment, subjects showed significant immune remodeling, with reduced expression of CTLA-4 (cytotoxin T lymphocyte–associated antigen 4) and elevated proinflammatory cytokine responses to malaria parasite antigens. The challenge in the longer term could be that restored immune responsiveness might increase the prevalence of inflammatory diseases.
Proc. Nat. Acad. Sci. 10.1073/pnas.1604570113 (2016).
[1]: pending:yes
Deworming
Proinflammatory cytokine
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