Eotaxin‐1 is involved in parasite clearance during chronic filarial infection

Gentil, Katrin; Lentz, Christian S.; Rai, Rajeev; Muhsin, Muhsin; Kamath, Ajit; Mutluer, Ö.; Specht, Sabine; Hübner, Marc P.; Hoerauf, Achim

doi:10.1111/pim.12079

Cited by 18 publications

(16 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3d), despite the fact that eosinophil numbers in the TC were comparable between the two infected groups of mice (Fig. 2d), confirming previous results which showed that eosinophil migration to the site of infection is independent of eotaxin-1 secretion (Gentil et al 2014). Levels of granzyme B were equal between infected WT and IL-17A −/− mice (Fig.…”

Section: Resultssupporting

confidence: 89%

Absence of IL-17A in Litomosoides sigmodontis-infected mice influences worm development and drives elevated filarial-specific IFN-γ

et al. 2018

View full text Add to dashboard Cite

Lymphatic filariasis, onchocerciasis and loiasis are widespread neglected tropical diseases causing serious public health problems and impacting the socio-economic climate in endemic communities. More than 100 million people currently suffer from filarial infections but disease-related symptoms and infection-induced immune mechanisms are still ambiguous. Although most infected individuals have dominant Th2 and regulatory immune responses leading to a homeostatic regulated state, filarial-induced overt pathology like lymphedema, dermal pathologies or blindness can occur. Interestingly, besides dominant Th2 and regulatory T cell activation, increased Th17-induced immune responses were associated with filarial infection and overt helminth-induced pathology in humans. However, the immunological mechanisms of Th17 cells and the release of IL-17A during filarial infections remain unclear. To decipher the role of IL-17A during filarial infection, we naturally infected IL-17A−/− and wildtype C57BL/6 mice with the rodent filariae Litomosoides sigmodontis and analysed parasite development and immune alterations. Our study reveals that infected IL-17A-deficient C57BL/6 mice present reduced worm burden on days 7 and 28 p.i. but had longer adult worms on day 28 p.i. in the thoracic cavity (TC), the site of infection. In addition, infiltration of CD4+ T cells, CD4+Foxp3+ regulatory T and functional CD4+Rorγt+pStat3+ Th17 cells in the TC was reduced in IL-17A-deficient mice accompanied by reduced eotaxin-1 and CCL17 levels. Furthermore, mediastinal lymph node cells isolated from IL-17A−/− mice showed increased filarial-specific IFN-γ but not IL-4, IL-6, or IL-21 secretion. This study shows that Th17 signalling is important for host immune responses against filarial infection but appears to facilitate worm growth in those that reach the TC.Electronic supplementary materialThe online version of this article (10.1007/s00436-018-5959-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Resultssupporting

confidence: 89%

Absence of IL-17A in Litomosoides sigmodontis-infected mice influences worm development and drives elevated filarial-specific IFN-γ

et al. 2018

View full text Add to dashboard Cite

show abstract

“…These cells rapidly kill parasites that have been damaged by anthelmintic drugs, and this may trigger a more vigorous proinflammatory response that results in AEs. This hypothesis is supported by the finding that eotaxin-1–deficient mice have reduced eosinophil responses to TLR2 activation and filarial antigen exposure, and the finding that macrophages from these mice produce less IL-6 [ 29 ]. Additional research will be needed to understand the apparent link between eotaxin-1 and AEs.…”

Section: Discussionmentioning

confidence: 93%

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis

Andersen

Kumar

Curtis

et al. 2017

The Journal of Infectious Diseases

View full text Add to dashboard Cite

show abstract

“…Thus, mice on a semi-resistant 129/SvJ background have an increased L. sigmodontis worm burden in the absence of the eosinophil products eosinophil peroxidase (EPO) and major basic protein (MBP) [32]. Similarly, eotaxin1-deficient mice had an increased L. sigmodontis adult worm burden [33]. Lack of the type 2 cytokine IL-5, which is also essential for eosinophil generation and survival, was previously shown to impair adult worm clearance during L. sigmodontis infection [34–37].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility to L. sigmodontis infection is highest in animals lacking IL-4R/IL-5 compared to single knockouts of IL-4R, IL-5 or eosinophils

et al. 2019

View full text Add to dashboard Cite

Background Mice are susceptible to infections with the rodent filarial nematode Litomosoides sigmodontis and develop immune responses that resemble those of human filarial infections. Thus, the L. sigmodontis model is used to study filarial immunomodulation, protective immune responses against filariae and to screen drug candidates for human filarial diseases. While previous studies showed that type 2 immune responses are protective against L. sigmodontis , the present study directly compared the impact of eosinophils, IL-5, and the IL-4R on the outcome of L. sigmodontis infection. Methods Susceptible wildtype (WT) BALB/c mice, BALB/c mice lacking eosinophils (dblGATA mice), IL-5 −/− mice, IL-4R −/− mice and IL-4R −/− /IL-5 −/− mice were infected with L. sigmodontis . Analyses were performed during the peak of microfilaremia in WT animals (71 dpi) as well as after IL-4R −/− /IL-5 −/− mice showed a decline in microfilaremia (119 dpi) and included adult worm counts, peripheral blood microfilariae levels, cytokine production from thoracic cavity lavage, the site of adult worm residence, and quantification of major immune cell types within the thoracic cavity and spleen. Results Our study reveals that thoracic cavity eosinophil numbers correlated negatively with the adult worm burden, whereas correlations of alternatively activated macrophage (AAM) numbers with the adult worm burden (positive correlation) were likely attributed to the accompanied changes in eosinophil numbers. IL-4R −/− /IL-5 −/− mice exhibited an enhanced embryogenesis achieving the highest microfilaremia with all animals becoming microfilariae positive and had an increased adult worm burden combined with a prolonged adult worm survival. Conclusions These data indicate that mice deficient for IL-4R −/− /IL-5 −/− have the highest susceptibility for L. sigmodontis infection, which resulted in an earlier onset of microfilaremia, development of microfilaremia in all animals with highest microfilariae loads, and an extended adult worm survival. Electronic supplementary material The online version of this article (10.1186/s13071-019-3502-z) contains supplementary material, which is available to authorized users.

show abstract

Eotaxin‐1 is involved in parasite clearance during chronic filarial infection

Cited by 18 publications

References 58 publications

Absence of IL-17A in Litomosoides sigmodontis-infected mice influences worm development and drives elevated filarial-specific IFN-γ

Absence of IL-17A in Litomosoides sigmodontis-infected mice influences worm development and drives elevated filarial-specific IFN-γ

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis

Susceptibility to L. sigmodontis infection is highest in animals lacking IL-4R/IL-5 compared to single knockouts of IL-4R, IL-5 or eosinophils

Contact Info

Product

Resources

About