Patent Filarial Infection Modulates Malaria-Specific Type 1 Cytokine Responses in an IL-10-Dependent Manner in a Filaria/Malaria-Coinfected Population

One third of the human population is infected with helminth parasites. To promote their longevity and to limit pathology, helminths have developed several strategies to suppress the immune response of their host. As this immune suppression also acts on unrelated third-party Ags, a preexisting helminth infection may interfere with vaccination efficacy. In this study, we show that natural infection with Litomosoides sigmodontis suppressed the humoral response to thymus-dependent but not to thymus-independent model Ags in C57BL/6 mice. Thereby, we provide evidence that reduced humoral responses were mediated by interference with Th cell function rather than by direct suppression of B cells in L. sigmodontis-infected mice. We directly demonstrate suppression of Ag-specific proliferation in OVA-specific Th cells after adoptive transfer into L. sigmodontis-infected mice that led to equally reduced production of OVA-specific IgG. Transferred Th cells displayed increased frequencies of Foxp3+ after in vivo stimulation within infected but not within naive mice. Helminth-mediated suppression was induced by established L. sigmodontis infections but was completely independent of the individual worm burden. Using DEREG mice, we rule out a central role for host-derived regulatory T cells in the suppression of transferred Th cell proliferation. In contrast, we show that L. sigmodontis-induced, host-derived IL-10 mediated Foxp3 induction in transferred Th cells and significantly contributed to the observed Th cell hypoproliferation within infected mice.

show abstract

“…Also, human studies strongly support the notion that IL-10 is a key mediator of nematode-induced immune suppression (46)(47)(48)(49).…”

Section: Discussionmentioning

confidence: 55%

Pathogenic Nematodes Suppress Humoral Responses to Third-Party Antigens In Vivo by IL-10–Mediated Interference with Th Cell Function

Hartmann

Haben

Fleischer

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Immunopathologies such as asthma, autoimmune diseases, and inflammatory bowel diseases are all reduced in prevalence in areas where helminth disease is endemic, and direct effects of helminth infections on the suppression of disease have been shown in clinical trials for inflammatory bowel diseases. malaria are both endemic, PBMCs from filaria-infected subjects produced less IL-12p70, IL-17A, and IFN-␥ but more IL-10 in response to malaria antigen (196,197), consistent with diminished IL-12 responses from filariasis patients stimulated with malarial antigen (198).…”

Section: Coinfection With Helminthsmentioning

confidence: 75%

Helminth Infections and Host Immune Regulation

2012

View full text Add to dashboard Cite

SUMMARY Helminth parasites infect almost one-third of the world's population, primarily in tropical regions. However, regions where helminth parasites are endemic record much lower prevalences of allergies and autoimmune diseases, suggesting that parasites may protect against immunopathological syndromes. Most helminth diseases are spectral in nature, with a large proportion of relatively asymptomatic cases and a subset of patients who develop severe pathologies. The maintenance of the asymptomatic state is now recognized as reflecting an immunoregulatory environment, which may be promoted by parasites, and involves multiple levels of host regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. Currently, there is much interest in whether helminth-associated immune regulation may ameliorate allergy and autoimmunity, with investigations in both laboratory models and human trials. Understanding and exploiting the interactions between these parasites and the host regulatory network are therefore likely to highlight new strategies to control both infectious and immunological diseases.

show abstract

“…The impact of filarial infections on antimalarial immunity has been characterized in detail in Africa, with an IL-10-dependent decrease in IL-12p70, interferon (IFN)-γ, and IFN-γ-induced protein 10 (IP-10) responses upon T-cell stimulation with malarial antigens, [78][79][80] but no data are available for chronic, mostly undiagnosed and untreated M. ozzardi infections in the Amazon.…”

Section: A Patchy Geographic Distributionmentioning

confidence: 99%

Mansonella ozzardi: a neglected New World filarial nematode

Lima

Aybar

Juri

et al. 2016

Pathogens and Global Health

View full text Add to dashboard Cite

Mansonella ozzardi (Nematoda: Onchocercidae) is an understudied filarial nematode, originally described by Patrick Manson in 1897, that can be transmitted by two families of dipteran vectors, biting midges (most of them members of the genus Culicoides) and black flies (genus Simulium). With a patchy geographic distribution from southern Mexico to northwestern Argentina, human infection with M. ozzardi is highly prevalent in some of the Caribbean islands, along riverine communities in the Amazon Basin, and on both sides of the border between Bolivia and Argentina. There is no clinical entity unequivocally associated with M. ozzardi infection, although fever, arthralgia, headache, cold lower extremities, and itchy cutaneous rashes are occasionally mentioned in case report series. More recently, ocular manifestations (especially keratitis) have been associated with mansonelliasis, opening an important area of investigation. Here, we briefly review the biology, epidemiology, pathogenesis, and clinical aspects of M. ozzardi infection and point to some existing knowledge gaps, aiming to stimulate a research agenda to help filling them. IntroductionMansonella ozzardi (Nematoda: Onchocercidae) is one of the several filarial nematodes that infect humans. This relatively unknown parasite has a patchy geographic distribution across Latin America and the Caribbean, from southern Mexico to northwestern Argentina. Most infected people, regardless of the parasite density, are asymptomatic or have few symptoms. As a consequence, infections with M. ozzardi usually remain undiagnosed and untreated. Ill-defined and unspecific symptoms such as fever, arthralgia, headache, cold lower extremities, and itchy cutaneous rashes are occasionally reported by patients, but whether they are caused by M. ozzardi infection remains to be determined. Nevertheless, ocular manifestations potentially associated with mansonelliasis, especially keratitis, have attracted substantial interest from ophthalmologists in recent years. Here, we summarize key biological, epidemiological, and clinical aspects of M. ozzardi infection. We explore recent developments in pathogenesis, laboratory diagnosis, and chemotherapy and discuss the potential public health impact of this highly prevalent but largely neglected New World parasite. Biological featuresThree filarial nematodes of the genus Mansonella are known to cause human mansonelliasis: Mansonella streptocerca, which is endemic to Africa; Mansonella perstans, which is commonly found in Africa but also occurs in South America; and M. ozzardi, which is found exclusively in the Americas and the Caribbean islands.1 Only humans appear to be naturally infected with M. ozzardi; African patas monkeys (Erythrocebus patas), but not chimpanzees, rhesus, capuchin, or squirrel monkeys, are susceptible to experimental infection with this nematode. 4 Several decades later, Orihel and Eberhard described the elusive adult male and female worms recovered from experimentally infected patas monkeys. 2Natural infection with M. ...

show abstract

Patent Filarial Infection Modulates Malaria-Specific Type 1 Cytokine Responses in an IL-10-Dependent Manner in a Filaria/Malaria-Coinfected Population

Cited by 59 publications

References 71 publications

Pathogenic Nematodes Suppress Humoral Responses to Third-Party Antigens In Vivo by IL-10–Mediated Interference with Th Cell Function

Pathogenic Nematodes Suppress Humoral Responses to Third-Party Antigens In Vivo by IL-10–Mediated Interference with Th Cell Function

Helminth Infections and Host Immune Regulation

Mansonella ozzardi: a neglected New World filarial nematode

Contact Info

Product

Resources

About