CENTRE MERSENNE Peer Community Journal is a member of the Centre Mersenne for Open Scientific Publishing http:// www.centre-mersenne.org/ e-ISSN 2804-3871 Peer Community Journal Section: Infections RESEARCH ARTICLE Published 2023-02-08 Cite as Moana Peylhard, David Berthier, Guiguigbaza-Kossigan Dayo, Isabelle Chantal, Souleymane Sylla, Sabine Nidelet, Emeric Dubois, Guillaume Martin, Guilhem Sempéré, Laurence Flori and Sophie Thévenon (2023) Whole blood transcriptome profiles of trypanotolerant and trypanosusceptible cattle highlight a differential modulation of metabolism and immune response during infection by Trypanosoma congolense, Peer Community Journal, 3: e17. Correspondence sophie.thevenon@cirad.fr Peer-review Peer reviewed and recommended by PCI Infections, https://doi.org/10.24072/pci. infections.100008 This article is licensed under the Creative Commons Attribution 4.0 License. Whole blood transcriptome profiles of trypanotolerant and trypanosusceptible cattle highlight a differential modulation of metabolism and immune response during infection by Trypanosoma congolense Moana Peylhard , 1,2 , David Berthier , 1,2 , Guiguigbaza-Kossigan Dayo , 3 , Isabelle Chantal , 1,2 , Souleymane Sylla 3 , Sabine Nidelet 4 , Emeric Dubois , 4 , Guillaume Martin , 5,6 , Guilhem Sempéré , 1,2 , Laurence Flori , 7 , and Sophie Thévenon , 1,2 Volume 3 (2023), article e17 https://doi.org/10.24072/pcjournal.239 Abstract Animal African trypanosomosis, caused by blood protozoan parasites transmitted mainly by tsetse flies, represents a major constraint for millions of cattle in sub-Saharan Africa. Exposed cattle include trypanosus- ceptible indicine breeds, severely affected by the disease, and West African taurine breeds called trypanotol- erant owing to their ability to control parasite development, survive and grow in enzootic areas. Until now the genetic basis of trypanotolerance remains unclear. Here, to improve knowledge of the biological pro- cesses involved in trypanotolerance versus trypanosusceptibility, we identified bovine genes differentially expressed in five West African cattle breeds during an experimental infection by Trypanosoma congolense and their biological functions. To this end, whole blood genome-wide transcriptome of three trypanotoler- ant taurine breeds (N’Dama, Lagune and Baoulé), one susceptible zebu (Zebu Fulani) and one African taurine x zebu admixed breed (Borgou) were profiled by RNA sequencing at four time points, one before and three during infection. As expected, infection had a major impact on cattle blood transcriptome regardless of the breed. The functional analysis of differentially expressed genes over time in each breed confirmed an early activation of the innate immune response, followed by an activation of the humoral response and an in- hibition of T cell functions at the chronic stage of infection. More importantly, we highlighted overlooked features, such as a strong disturbance in host metabolism and cellular energy production that differentiates trypanotolerant and trypanosusceptible breeds. N’Dama breed showed the earliest regulation of immune response, associated with a strong activation of cellular energy production, also observed in Lagune, and to a lesser extent in Baoulé. Susceptible Zebu Fulani breed differed from other breeds by the strongest modification in lipid metabolism regulation. Overall, this study provides a better understanding of the bi- ological mechanisms at work during infection, especially concerning the interplay between immunity and metabolism that seems differentially regulated depending on the cattle breeds. 1 CIRAD, UMR INTERTRYP, F-34398 Montpellier, France, 2 INTERTRYP, Univ. Montpellier, CIRAD, IRD, Montpellier, France, 3 Centre International de Recherche-Développement sur l’Elevage en zone Subhumide (CIRDES), 01 BP 454, Bobo-Dioulasso 01, Burkina Faso, 4 Montpellier GenomiX, France Génomique, Montpellier, France, 5 CIRAD, UMR AGAP Institut, F-34398 Montpel- lier, France, 6 UMR AGAP Institut, Univ Montpellier, CIRAD, INRAE, Institut Agro, Montpellier, France, 7 SELMET, INRAE, CIRAD, Montpellier Supagro, University of Montpellier, Montpellier, France