Surfing on the waves of the human γδ T cell ontogenic sea.

While γδ T cells are present virtually in all vertebrates, there is a remarkable lack of conservation of the TRG and TRD loci underlying the generation of the γδ T cell receptor (TCR), which is associated with the generation of species-specific γδ T cells. A prominent example is the human phosphoantigen-reactive Vγ9Vδ2 T cell subset that is absent in mice. Murine γδ thymocyte cells were among the first immune cells identified to follow a wave-based layered development during embryonic and early life, and since this initial observation, in-depth insight has been obtained in their thymic ontogeny. By contrast, less is known about the development of human γδ T cells, especially regarding the generation of γδ thymocyte waves. Here, after providing an overview of thymic γδ wave generation in several vertebrate classes, we review the evidence for γδ waves in the human fetal thymus, where single-cell technologies have allowed the breakdown of human γδ thymocytes into functional waves with important TCR associations. Finally, we discuss the possible mechanisms contributing to the generation of waves of γδ thymocytes and their possible significance in the periphery.

Identification of distinct functional thymic programming of fetal and pediatric human γδ thymocytes via single-cell analysis.

Developmental thymic waves of innate-like and adaptive-like γδ T cells have been described, but the current understanding of γδ T cell development is mainly limited to mouse models. Here, we combine single cell (sc) RNA gene expression and sc γδ T cell receptor (TCR) sequencing on fetal and pediatric γδ thymocytes in order to understand the ontogeny of human γδ T cells. Mature fetal γδ thymocytes (both the Vγ9Vδ2 and nonVγ9Vδ2 subsets) are committed to either a type 1, a type 3 or a type 2-like effector fate displaying a wave-like pattern depending on gestation age, and are enriched for public CDR3 features upon maturation. Strikingly, these effector modules express different CDR3 sequences and follow distinct developmental trajectories. In contrast, the pediatric thymus generates only a small effector subset that is highly biased towards Vγ9Vδ2 TCR usage and shows a mixed type 1/type 3 effector profile. Thus, our combined dataset of gene expression and detailed TCR information at the single-cell level identifies distinct functional thymic programming of γδ T cell immunity in human.

Multi-country investigation of the diversity and associated microorganisms isolated from tick species from domestic animals, wildlife and vegetation in selected african countries.

In many areas of Africa, recent studies highlighted the great impact of ticks on animal and human health throughout the continent. On the other hand, very limited information on the bacterial endosymbionts of the African ticks and their pattern of co-infections with other bacteria are found in literature, notwithstanding their pivotal role in tick survival and vector efficiency. Thus, we investigated the distribution of selected pathogenic and symbiotic bacteria in hard ticks collected from wild, domestic animals and from vegetation in various ecological zones in Africa and their co-occurrence in the same tick host. Overall, 339 hard ticks were morphologically identified as belonging to the genera Amblyomma, Dermacentor, Hyalomma, Haemaphysalis, Ixodes and Rhipicephalus. Molecular screening provided information on pathogens circulation in Africa, detecting spotted fever group rickettsiae, Anaplasma spp., Ehrlichia ruminantium, Borrelia garinii, Babesia spp., Theileria spp. and Coxiella burnetii. Furthermore, our work provides insights on the African scenario of tick-symbiont associations, revealing the presence of Coxiella, Francisella and Midichloria across multiple tick populations. Coxiella endosymbionts were the most prevalent microorganisms, and that with the broadest spectrum of hosts, being detected in 16 tick species. Francisella was highly prevalent among the Hyalomma species tested and correlated negatively with the presence of Coxiella, showing a potential competitive interaction. Interestingly, we detected a positive association of Francisella with Rickettsia in specimens of Hy. rufipes, suggesting a synergistic interaction between them. Finally, Midichloria was the most prevalent symbiont in Rhipicephalus sanguineus sensu lato from Egypt.