Transcriptomic Profile of Canine DH82 Macrophages Infected by Leishmania infantum Promastigotes with Different Virulence Behavior.

Alicia Mas,Pilar Horcajo,Juan F Alzate,Abel Martínez-Rodrigo,Javier Carrión,José Antonio Orden,Gustavo Domínguez-Bernal

doi:10.3390/ijms23031466

Abstract

Zoonotic visceral leishmaniosis caused by Leishmania infantum is an endemic disease in the Mediterranean Basin affecting mainly humans and dogs, the main reservoir. The leishmaniosis outbreak declared in the Community of Madrid (Spain) led to a significant increase in human disease incidence without enhancing canine leishmaniosis prevalence, suggesting a better adaptation of the outbreak’s isolates by other host species. One of the isolates obtained in the focus, IPER/ES/2012/BOS1FL1 (BOS1FL1), has previously demonstrated a different phenotype than the reference strain MCAN/ES/1996/BCN150 (BCN150), characterized by a lower infectivity when interacting with canine macrophages. Nevertheless, not enough changes in the cell defensive response were found to support their different behavior. Thus, we decided to investigate the molecular mechanisms involved in the interaction of both parasites with DH82 canine macrophages by studying their transcriptomic profiles developed after infection using RNA sequencing. The results showed a common regulation induced by both parasites in the phosphoinositide-3-kinase–protein kinase B/Akt and NOD-like receptor signaling pathways. However, other pathways, such as phagocytosis and signal transduction, including tumor necrosis factor, mitogen-activated kinases and nuclear factor-κB, were only regulated after infection with BOS1FL1. These differences could contribute to the reduced infection ability of the outbreak isolates in canine cells. Our results open a new avenue to investigate the true role of adaptation of L. infantum isolates in their interaction with their different hosts.

Highlights

Leishmaniases are parasitic diseases caused by different species of the genus Leishmania, which are transmitted via female phlebotomine sand flies [1]
We investigated the interaction of BCN150 and BOS1FL1 with canine monocytes and macrophages derived from peripheral blood [19]
To the best of the authors’ knowledge, no previous studies have used RNA sequencing (RNA-seq) to analyze the interaction of L. infantum with cells of canine origin, and it is difficult to translocate the miscellaneous results obtained with other host and parasite species to comprehensively describe the Leishmania-infected canine macrophage response

Summary

Introduction

Leishmaniases are parasitic diseases caused by different species of the genus Leishmania, which are transmitted via female phlebotomine sand flies [1]. In the Mediterranean Basin, zoonotic visceral leishmaniosis (ZVL) due to Leishmania infantum is considered endemic and constitutes a major public health challenge, as it affects both humans and dogs, the main reservoir [2]. In 2009, an important human leishmaniosis outbreak was declared in the Community of Madrid (Spain), resulting in a dramatic increase in its incidence, with more than 700 cases in this region alone until 2016 [4]. This outbreak has attracted the interest of the scientific community, as it presents interesting singularities. Seroprevalence and xenodiagnostic studies confirmed the establishment of a mainly sylvatic transmission cycle, independent of canids [7], with lagomorphs as alternative reservoirs for the parasite [8,9]

Methods

Results

Conclusion