FLAgellum Member 8 modulates extravascular trypanosome distribution in the mammalian host

The African trypanosome flagellum is an essential organelle in multiple aspects of the parasites development. Here, we investigated the role of a flagellar protein termed FLAgellar Member 8 (FLAM8) that is specifically distributed along the entire flagellum in trypanosomes stages of the vertebrate host. Analyses of knockdown and knockout trypanosomes demonstrated that FLAM8 is not essential in vitro for survival, growth, motility and slender to stumpy differentiation. Functional investigations in experimental infections showed that FLAM8-deprived trypanosomes are able to establish and maintain the infection in the blood circulation, and to differentiate into insect transmissible forms. However, quantitative bioluminescence imaging revealed that FLAM8-null parasites exhibit an impaired dissemination in the extravascular compartment, that is partially restored by the addition of a single rescue copy of FLAM8. Interestingly, among all dissected organs scrutinized individually, only the skin of mice infected with FLAM8-deprived parasites showed a significant reduction in extravascular trypanosome population as compared to mice infected with parental controls. To our knowledge, FLAM8 is the first example of a flagellar protein that modulates T. brucei parasite distribution in the host tissues, contributing to the maintenance of extravascular parasite populations in mammalian anatomical niches, especially in the skin. Take awayO_LIFLAM8 is dispensable in vitro for survival, growth, motility and differentiation of T. brucei. C_LIO_LIFLAM8 depletion does not affect parasitemia and bloodstream form differentiation in vivo. C_LIO_LIFLAM8 modulates the extravascular dissemination of trypanosomes in the mammalian host, especially in the skin. C_LI