The central adaptor molecule TRIF influences L. sigmodontis worm development
Worldwide approximately 68 million people are infected with lymphatic filariasis (Lf), provoked by Wuchereria bancrofti, Brugia malayi and Brugia timori. This disease can lead to massive swelling of the limbs (elephantiasis) and disfigurement of the male genitalia (hydrocele). Filarial induced immune regulation is characterised by dominant type 2 helper T cell and regulatory immune responses. In vitro studies have provided evidence that signalling via Toll-like receptor-mediated pathways is triggered by filarial associated factors. Nevertheless, until now, less is known about the role of the adapter molecule TRIF during in vivo infections. Here, we used the rodent-specific nematode Litomosoides sigmodontis to investigate the role of TLR signalling and the corresponding downstream adapter and regulatory molecules TRIF, MyD88, IRF1 and IRF3 during an ongoing infection in semi-susceptible C57BL/6 mice. Interestingly, lack of the central adapter molecule TRIF led to higher worm burden and reduced overall absolute cell numbers in the thoracic cavity (the site of infection) 30 days post-infection. In addition, frequencies of macrophages and lymphocytes in the TC were increased in infected TRIF−/− C57BL/6 mice, whereas frequencies of eosinophils, CD4+ and CD8+ T cells were reduced. Nevertheless, cytokine levels and regulatory T cell populations remained comparable between TRIF-deficient and wildtype C57BL/6 mice upon 30 days of L. sigmodontis infection. In summary, this study revealed a crucial role of the adapter molecule TRIF on worm recovery and immune cell recruitment into the site of infection 30 days upon L. sigmodontis infection in C57BL/6 mice.
KeywordsLymphatic filariasis Litomosoides sigmodontis TLR signalling Worm burden Adapter molecule TRIF Semi-susceptible C57BL/6 mice
eosinophil cationic protein
interferon regulatory receptor
L. sigmodontis worm antigen
mediastinal lymph nodes
myeloid differentiation primary response gene 88
pattern recognition receptors
regulatory T cells
Toll/interleukin-1 receptor domain-containing adapter-inducing interferon-β
Special thanks to Ö. Mutluer and K. Wiszniewsky (IMMIP) for the excellent technical assistance.
LEL and AH conceived and designed the study. AW, VK and SS performed the experiments. HW provided materials and mouse lines. AW, KA, MR and LEL analysed and interpreted data sets. AW, LEL and MR wrote the manuscript which was then critically assessed and amended by HW, SW and AH. All authors read and approved the final manuscript.
LEL is a recipient of DFG funding within the African-German Cooperation Projects in Infectiology (LA 2746/1-1, LA 2746/2-1). AH is a member of the Excellence Cluster Immunosensation (DFG, EXC 1023) and AH and LEL are members of the German Centre of Infectious Disease (DZIF).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethics approval and consent to participate
All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.
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