Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-β production

Eliáš, Daniel; Britton, Sven; Aseffa, Abraham; Engers, Howard; Akuffo, Hannah

doi:10.1016/j.vaccine.2008.04.083

Cited by 182 publications

(167 citation statements)

References 32 publications

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“…Yet, most parasitic worms live in the gut and are therefore not proximal to the site where injection-based vaccines are delivered. Although some findings indicate that intestinal worms have more systemic effects on immunity (7,8,37,38), evidence that intestinal nematodes modulate immune response in tissue distal to the worms and thereby impair immune responses to vaccination and secondary infections is scarce and remains questioned (12,26,39,40).…”

Section: Discussionmentioning

confidence: 99%

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Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

Obieglo

Feng

Bollampalli

et al. 2016

The Journal of Immunology

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Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette–Guérin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4+ T cell priming in both the spleen and skin-draining lymph nodes. Furthermore, H. polygyrus infection reduced the magnitude of delayed-type hypersensitivity (DTH) to PPD in the skin. Consequently, H. polygyrus–infected mice challenged with BCG had a higher mycobacterial load in the liver compared with worm-free mice. The excretory–secretory product from H. polygyrus (HES) was found to dampen IFN-γ production by mycobacteria-specific CD4+ T cells. This inhibition was dependent on the TGF-βR signaling activity of HES, suggesting that TGF-β signaling plays a role in the impaired Th1 responses observed coinfection with worms. Similar to results with mycobacteria, H. polygyrus–infected mice displayed an increase in skin parasite load upon secondary infection with Leishmania major as well as a reduction in DTH responses to Leishmania Ag. We show that a nematode confined to the gut can mute T cell responses to mycobacteria and impair control of secondary infections distal to the gut. The ability of intestinal helminths to reduce DTH responses may have clinical implications for the use of skin test–based diagnosis of microbial infections.

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Section: Discussionmentioning

confidence: 99%

“…Accordingly, worm infection is proposed to impair immune responses that control mycobacteria (4)(5)(6). Infection with worms has also been associated with a reduced ability to respond to BCG vaccination (7,8). Geographically, areas of high TB incidence and poor TB vaccine efficacy typically have a high prevalence of intestinal helminth infections (9).…”

mentioning

confidence: 99%

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

Obieglo

Feng

Bollampalli

et al. 2016

The Journal of Immunology

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“…Interestingly, it has also been shown that helminth infections can affect responses to unrelated Ag, such as those expressed in vaccines or by other pathogens [5]. Geohelminth infections have, for example, been associated with reduced immune responses to BCG vaccination [6] and to the cholera vaccine [7]. With respect to co-infections, epidemiological studies in areas where helminths and Plasmodium spp.…”

Section: Cd25mentioning

confidence: 99%

Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum

et al. 2010

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Chronic helminth infections induce T-cell hyporesponsiveness, which may affect immune responses to other pathogens or to vaccines. This study investigates the influence of Treg activity on proliferation and cytokine responses to BCG and Plasmodium falciparum-parasitized RBC in Indonesian schoolchildren. Geohelminth-infected children's in vitro T-cell proliferation to either BCG or pRBC was reduced compared to that of uninfected children. Although the frequency of CD41 T cells was similar regardless of infection status, the suppressive activity differed between geohelminth-infected and geohelminthuninfected groups: Ag-specific proliferative responses increased upon CD4 1 CD25 hi T-cell depletion in geohelminth-infected subjects only. In addition, IFN-c production in response to both BCG and parasitized RBC was increased after removal of CD4These data demonstrate that geohelminth-associated Treg influence immune responses to bystander Ag of mycobacteria and plasmodia. Geohelminth-induced immune modulation may have important consequences for co-endemic infections and vaccine trials.

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“…Approximately 1 billion people are infected with one or more helminths, of which schistosomiasis, caused by trematodes of the genus Schistosoma mansoni (S. mansoni), affects about 207 million individuals (6). Human studies on coinfected individuals suggest that infection with helminths compromise protection conferred by M. bovis Bacillus Calmette-Guerin (BCG) vaccination (7)(8)(9) and may be associated with increased TB reactivation rates in HIV-infected patients (10). In experimental models, mice chronically infected with S. mansoni have increased susceptibility to M. bovis BCG systemic infection, accompanied by decreased M. bovis BCG-specific Th1 responses (11).…”

Section: Introductionmentioning

confidence: 99%

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

Monin¹,

Griffiths²,

Lam³

et al. 2015

Journal of Clinical Investigation

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Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-β production

Cited by 182 publications

References 32 publications

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

Chronic Gastrointestinal Nematode Infection Mutes Immune Responses to Mycobacterial Infection Distal to the Gut

Regulatory T cells in human geohelminth infection suppress immune responses to BCG and Plasmodium falciparum

Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

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