Effect of helminth-induced immunity on infections with microbial pathogens

Salgame, Padmini; Yap, George; Gause, William C.

doi:10.1038/ni.2736

Cited by 249 publications

(289 citation statements)

References 122 publications

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“…Plasmodium-infected individuals with hepatitis B virus infection were more likely to be asymptomatic and to have lower levels of parasitemia, possibly through an increase in the production of IFN-g levels induced by viral infection that can contribute to Plasmodium clearance in the liver [59]. Coinfection with soil-transmitted helminths may alter susceptibility to clinical malaria by activating T H 2 cytokines and immunoregulatory pathways that downregulate effector functions involved in resistance to malaria [60]. HIV can also impair lymphocyte functions against malaria infection [61].…”

mentioning

confidence: 99%

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

Galatas

Bassat

Mayor

2016

Trends in Parasitology

115

122

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With malaria elimination back on the international agenda, programs face the challenge of targeting all Plasmodium infections, not only symptomatic cases. As asymptomatic individuals are unlikely to seek treatment, they are missed by passive surveillance while remaining infectious to mosquitoes, thus acting as silent reservoirs of transmission. To estimate the risk of asymptomatic infections in various phases of malaria elimination, we need a deeper understanding of the underlying mechanisms favoring carriage over disease, which may involve both pathogen and host factors. Here we review our current knowledge on the determinants leading to Plasmodium falciparum symptomless infections. Understanding the host-pathogen interactions that are most likely to affect transitions between malaria disease states could guide the development of tools to tackle asymptomatic carriers in elimination settings. Being AsymptomaticPeaceful coexistence with the infected host, rarely causing clinical symptoms, is a common but poorly understood phenomenon that occurs for many human pathogens [1]. Because such asymptomatic cases of infection occur without eventual overt symptoms, they do not come to clinical attention, thus representing a large hidden reservoir of active infection that permits their persistence and eventual spread to other human hosts. This is the case for many malaria infections in semi-immune individuals from endemic areas, which commonly cause a mild febrile illness or no apparent symptoms at all, while keeping parasite numbers at low densities [2] (Box 1).Carriage of asymptomatic malaria (see Glossary) infections, being at the same time difficult to detect and to manage, has considerable implications for the design and use of malaria elimination strategies. Symptomless infections that persist during the dry season in areas of seasonal transmission have been suggested to seed the malaria outbreaks after annual rains when mosquitoes reappear [3]. Similarly, asymptomatic parasitemia may potentially contribute to persistence of transmission in low-transmission settings [4]. However, the precise contribution of asymptomatic malaria to transmission in areas that have achieved substantial reductions in the malaria burden remains a matter of debate [5], as is the assumption that detecting and targeting these individuals for radical treatment, as opposed to using mass drug administration approaches, would be an efficient and effective tactic. Moreover, eradication in Europe, North America, and other parts of the world using no better diagnostics than microscopy [6] suggest that key determinants of success might not be finding the last parasite. From a practical point of view, the proportion of asymptomatic infections in certain situations and phases of malaria elimination may impose the need for modifications of detection methods (active versus passive case detection) [7] if, for example, symptom-based surveillance at health facilities is insufficient and mass blood surveys are necessary to inform the design of elimination i...

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mentioning

confidence: 99%

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

Galatas

Bassat

Mayor

2016

Trends in Parasitology

115

122

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“…M ore than 2 billion people worldwide suffer from intestinal helminth infections that often harm their host by destroying tissue integrity, feeding on blood, and suppressing the immune response to other infectious diseases (1)(2)(3). Helminths also severely impact on agriculture by widely infecting livestock throughout the developed and developing world (4,5).…”

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confidence: 99%

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

Bieren

Volpe

Kulagin

et al. 2015

The Journal of Immunology

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Infections with intestinal helminths severely impact on human and veterinary health, particularly through the damage that these large parasites inflict when migrating through host tissues. Host immunity often targets the motility of tissue-migrating helminth larvae, which ideally should be mimicked by anti-helminth vaccines. However, the mechanisms of larval trapping are still poorly defined. We have recently reported an important role for Abs in the rapid trapping of tissue-migrating larvae of the murine parasite Heligmosomoides polygyrus bakeri. Trapping was mediated by macrophages (MΦ) and involved complement, activating FcRs, and Arginase-1 (Arg1) activity. However, the receptors and Ab isotypes responsible for MΦ adherence and Arg1 induction remained unclear. Using an in vitro coculture assay of H. polygyrus bakeri larvae and bone marrow–derived MΦ, we now identify CD11b as the major complement receptor mediating MΦ adherence to the larval surface. However, larval immobilization was largely independent of CD11b and instead required the activating IgG receptor FcγRI (CD64) both in vitro and during challenge H. polygyrus bakeri infection in vivo. FcγRI signaling also contributed to the upregulation of MΦ Arg1 expression in vitro and in vivo. Finally, IgG2a/c was the major IgG subtype from early immune serum bound by FcγRI on the MΦ surface, and purified IgG2c could trigger larval immobilization and Arg1 expression in MΦ in vitro. Our findings reveal a novel role for IgG2a/c-FcγRI–driven MΦ activation in the efficient trapping of tissue-migrating helminth larvae and thus provide important mechanistic insights vital for anti-helminth vaccine development.

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“…As infecções por helmintos desencadeiam a liberação de citocinas e ativação de células do padrão Ta2 semelhantes em diferentes espécies de parasitos (Necator e Ancylostoma, Trichuris, Ascaris ou Cestoda) com resposta imune tanto inata quanto adaptativa (Salgame, Yap & Gause, 2013;Mishra, Palma, Bleich, et al, 2014;Hayes, Bancroft & Grencis, 2004).…”

Section: Papel Da Imunidade Inata E Adquirida Na Defesa Contra Os Parunclassified

“…Dentre essas células, as células dendríticas ativadas e outras células da resposta imune inata migram da lâmina própria e das placas de Peyers pelos vasos linfáticos para os linfonodos mesentéricos, onde ocorre estímulo para a resposta imune adaptativa com desvio para o padrão Ta2 e Treg. Há supressão da ativação de células e produção de citocinas do tipo Ta1 e Ta17 (Salgame, Yap & Gause, 2013;Mishra, Palma, Bleich, et al, 2014).…”

Section: Papel Da Imunidade Inata E Adquirida Na Defesa Contra Os Parunclassified

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Desvendando a resposta dos eosinófilos, dos neutrófilos e dos monócitos nas parasitoses intestinais, na asma e na associação de ambas em crianças

Ribeiro¹

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Effect of helminth-induced immunity on infections with microbial pathogens

Cited by 249 publications

References 122 publications

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

Malaria Parasites in the Asymptomatic: Looking for the Hay in the Haystack

Antibody-Mediated Trapping of Helminth Larvae Requires CD11b and Fcγ Receptor I

Desvendando a resposta dos eosinófilos, dos neutrófilos e dos monócitos nas parasitoses intestinais, na asma e na associação de ambas em crianças

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