GSE244972 The different impact of drug-resistant Leishmania on the transcription programs activated in neutrophils.

Contributors : M íriam Díaz-Varela ; Andrea Sánchez-Hidalgo ; Sandra Calderon-Copete ; Virginie Tacchini ; Tobias Shipley ; LadyGiovanna Ramírez ; Julien Marquis ; OlgaLucía Fernández ; Nancy Gore Saravia ; Fabienne Tacchini-CottierSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensDrug resistance threatens the effective control of infections, including parasitic diseases such as leishmaniases. Neutrophils are essential players in antimicrobial control, but their role in drug-resistant infections is poorly understood. Here, we evaluated human neutrophil response to clinical parasite strains having distinct natural drug susceptibility. We found that Leishmania antimony drug resistance significantly altered the expression of neutrophil genes, some of them transcribed by specific neutrophil subsets. Infection with drug-resistant parasites increased the expression of detoxification pathways and reduced the production of cytokines. Among these, the chemokine CCL3 was predominantly impacted, which resulted in an impaired ability of neutrophils to attract myeloid cells. Moreover, decreased myeloid recruitment when CCL3 levels are reduced was confirmed by blocking CCL3 in a mouse model. Collectively, these findings reveal that the interplay between naturally drug-resistant parasites and neutrophils modulates the infected skin immune microenvironment, revealing a key role of neutrophils in drug resistance.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research