Impairment of Tetanus-Specific Cellular and Humoral Responses following Tetanus Vaccination in Human Lymphatic Filariasis

Nookala, Suba; Srinivasan, Sundaram; Kaliraj, Perumal; Narayanan, R. B.; Nutman, Thomas B.

doi:10.1128/iai.72.5.2598-2604.2004

Cited by 111 publications

(87 citation statements)

References 33 publications

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“…In high-intensity human filarial infections, there is strong evidence that immune down-regulation extends beyond parasite specificities, spreading out to affect responses to vaccine Ags in vivo (51)(52)(53) and T cell stimulation in vitro (54). A more subtle consequence of such regulatory spreading may be the dampening of allergies in helminth-infected individuals (42,55,56).…”

Section: Discussionmentioning

confidence: 99%

Expansion of Foxp3+ Regulatory T Cells in Mice Infected with the Filarial Parasite Brugia malayi

McSorley

Harcus

Murray

et al. 2008

The Journal of Immunology

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Many helminths, including Brugia malayi, are able to establish long-lived infections in immunocompetent hosts. Growing evidence suggests that the immune system’s failure to eliminate parasites is at least partially due to the effects of regulatory T cells (Tregs). To test whether parasites may directly stimulate host regulatory activity, we infected mice with two key stages of B. malayi. Both mosquito-borne infective larvae and mature adults i.p. introduced were found to preferentially expand the proportion of CD25+Foxp3+ cells within the CD4+ T cell population. The induction of Foxp3 was accompanied by raised CD25, CD103, and CTLA-4 expression, and was shown to be an active process, which accompanied the introduction of live, but not dead parasites. CTLA-4 expression was also markedly higher on Foxp3− cells, suggesting anergized effector populations. Peritoneal lavage CD4+CD25+ cells from infected mice showed similar suppressive activity in vitro to normal splenic “natural” Tregs. Both B. malayi larvae and adults were also able to induce Foxp3 expression in adoptively transferred DO11.10 T cells, demonstrating that filarial infection can influence the development of T cells specific to a third party Ag. In addition, we showed that induction was intact in IL-4R-deficient animals, in the absence of a Th2 or alternatively activated macrophage response. We conclude that filarial infections significantly skew the balance of the host immune system toward Treg expansion and activation, in a manner dependent on live parasites but independent of a concomitant Th2 response.

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Section: Discussionmentioning

confidence: 99%

Expansion of Foxp3+ Regulatory T Cells in Mice Infected with the Filarial Parasite Brugia malayi

McSorley

Harcus

Murray

et al. 2008

The Journal of Immunology

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“…Exposure to pathogens and their products, and to helminths in particular, has been shown to protect against the development of autoimmune and allergic diseases in experimental animal models (7,8,10,23,25,26,28), and some evidence in support of this has been observed in human populations (3,8,10,23,29,30,31).…”

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confidence: 94%

Chronic Intestinal Helminth Infections Are Associated with Immune Hyporesponsiveness and Induction of a Regulatory Network

et al. 2010

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“…Coinfections may alter disease outcomes and affect both drug and vaccine efficacies (1,2). The majority of studies on coinfections have focused on interactions between malaria and chronic helminth infections.…”

mentioning

confidence: 99%

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

et al. 2016

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c Malaria and schistosomiasis coinfections are common, and chronic schistosomiasis has been implicated in affecting the severity of acute malaria. However, whether it enhances or attenuates malaria has been controversial due the lack of appropriately controlled human studies and relevant animal models. To examine this interaction, we conducted a randomized controlled study using the baboon (Papio anubis) to analyze the effect of chronic schistosomiasis on severe malaria. Two groups of baboons (n ‫؍‬ 8 each) and a schistosomiasis control group (n ‫؍‬ 3) were infected with 500 Schistosoma mansoni cercariae. At 14 and 15 weeks postinfection, one group was given praziquantel to treat schistosomiasis infection. Four weeks later, the two groups plus a new malaria control group (n ‫؍‬ 8) were intravenously inoculated with 10 5 Plasmodium knowlesi parasites and monitored daily for development of severe malaria. A total of 81% of baboons exposed to chronic S. mansoni infection with or without praziquantel treatment survived malaria, compared to only 25% of animals infected with P. knowlesi only (P ‫؍‬ 0.01). Schistosome-infected animals also had significantly lower parasite burdens (P ‫؍‬ 0.004) than the baboons in the P. knowlesi-only group and were protected from severe anemia. Coinfection was associated with increased spontaneous production of interleukin-6 (IL-6), suggesting an enhanced innate immune response, whereas animals infected with P. knowlesi alone failed to develop mitogen-driven tumor necrosis factor alpha and IL-10, indicating the inability to generate adequate protective and balancing immunoregulatory responses. These results indicate that chronic S. mansoni attenuates the severity of P. knowlesi coinfection in baboons by mechanisms that may enhance innate immunity to malaria. P olyparasitism is common in low-resource countries, especially in sub-Saharan Africa. Coinfections may alter disease outcomes and affect both drug and vaccine efficacies (1, 2). The majority of studies on coinfections have focused on interactions between malaria and chronic helminth infections. Interest in studying malaria and schistosomiasis, in particular, comes from the major overlap of the two diseases in areas where they are endemic and the fact that these infections account for a large proportion of global morbidity and mortality (3, 4). Because of the chronicity of schistosome infection, most studies have focused on its impact on susceptibility to clinical malaria.Studies on malaria and schistosomiasis coinfections in human and animal models have generated contradicting results. Although some animal studies have shown that chronic schistosomiasis protects against severe malaria (5), others have reported that a concurrent schistosome infection enhances the severity of malaria (6-10). Many factors may account for these differences, including mouse strain, duration and intensity of the helminth infection, Plasmodium strain or species, inoculum size, or route of malaria infection (skin or blood stage) (11). An important limitat...

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Impairment of Tetanus-Specific Cellular and Humoral Responses following Tetanus Vaccination in Human Lymphatic Filariasis

Cited by 111 publications

References 33 publications

Expansion of Foxp3+ Regulatory T Cells in Mice Infected with the Filarial Parasite Brugia malayi

Expansion of Foxp3+ Regulatory T Cells in Mice Infected with the Filarial Parasite Brugia malayi

Chronic Intestinal Helminth Infections Are Associated with Immune Hyporesponsiveness and Induction of a Regulatory Network

Protective Effect of Chronic Schistosomiasis in Baboons Coinfected with Schistosoma mansoni and Plasmodium knowlesi

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