Development of patent Litomosoides sigmodontis infections in semi-susceptible C57BL/6 mice in the absence of adaptive immune responses

Particle and Fibre Toxicology

Marc P. Hübner¹  Achim Hoerauf¹  Anna Wiszniewsky¹  Manuel Ritter¹  Jesuthas Ajendra¹  Laura E. Layland¹ 

[1] Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital of Bonn, Sigmund Freud Straße 25, Bonn 53105, Germany

关键词: Immune-regulation;    Patency;    C57BL/6;    Filariae;    Litomosoides sigmodontis;   

Others  :  1222165
DOI  :  10.1186/s13071-015-1011-2

 received in 2014-12-05, accepted in 2015-07-16,  发布年份 2015

【 摘 要 】

Background

One of the most advantageous research aspects of the murine model of filariasis, Litomosoides sigmodontis, is the availability of mouse strains with varying susceptibility to the nematode infection. In C57BL/6 mice, L. sigmodontis worms are largely eliminated in this strain by day 40 post-infection and never produce their offspring, microfilariae (Mf). This provides a unique opportunity to decipher potential immune pathways that are required by filariae to achieve a successful infection. In this study we tracked worm development and patency, the production of microfilariae and thus the transmission life-stage, in Rag2IL-2Rγ ^−/−mice which are deficient in T, B and NK cell populations.

Findings

Although worm burden was comparable between wildtype (WT) and Rag2IL-2Rγ ^−/−mice on d30, by day 72 post-infection, parasites in Rag2IL-2Rγ ^−/−mice were still in abundance, freely motile and all mice presented high quantities of Mf both at the site of infection, the thoracic cavity (TC), and in peripheral blood. Levels of cytokine (IL-4, IL-6, TNFα) and chemokine (MIP-2, RANTES, Eotaxin) parameters were generally low in the TC of infected Rag2IL-2Rγ ^−/− mice at both time-points. The frequency of neutrophils however was higher in Rag2IL-2Rγ ^−/− mice whereas eosinophils and macrophage populations, including alternatively activated macrophages, were elevated in WT controls.

Conclusion

Our data highlight that adaptive immune responses prevent the development of patent L. sigmodontis infections in semi-susceptible C57BL/6 mice and suggest that induction of such responses may offer a strategy to prevent transmission of human filariasis.

【 授权许可】

   
2015 Layland et al.

【 图 表 】

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