Although the role of regulatory T cells (Tregs) during malaria infection has been studied extensively, such studies have focused exclusively on the role of Treg during the blood stage of infection; little is known about the detailed mechanisms of Tregs and sporozoite deposition in the dermis by mosquito bites. In this paper we show that sporozoites introduced into the skin by mosquito bites increase the mobility of skin Tregs and dendritic cells (DCs). We also show differences in MHC class II and/or CD86 expression on skin-resident dendritic cell subtypes and macrophages. From the observed decrease of the number of APCs into draining lymph nodes, suppression of CD28 expression in conventional CD4 T cells, and a low homeostatic proliferation of skin-migrated CD4 T found in nude mice indicate that Tregs may play a fundamental role during the initial phase of malaria parasite inoculation into the mammalian host.
Bibliographical noteFunding Information:
We would like to thank Drs. Michael L. Dustin and Juan J. Lafaille for the critical review of this work. C57Bl/6.Foxp3-KI gfp/gfp mice and C57Bl/6.CD11c–YFP animals were a generous gift from Drs. Vijay K. Kuchroo and Mohamed Oukka (Harvard University, USA) and Dr. Michel C. Nussenzweig (Rockefeller University, USA), respectively. Dr. Gabriel Martins (Faculdade de Ciências da Universidade de Lisboa, Portugal) and M.Sc. Francisco Henriques (Cell Imaging Unit, Instituto Gulbenkian de Ciência, Portugal) helped with the imaging analysis. Ms. Fernanda G. Baptista and Ms. Ana Parreira prepared all mosquitos used in this manuscript. This work was partially supported by the FCT grant PTDC/EBB-BIO/115514/2009 and H.B.S. was a recipient of a CAPES–FCT travel grant 258/2010.
- Dendritic cell
- Plasmodium berghei
- Regulatory T cell