Identifying Bacterial and Host Factors Involved in the Interaction of Mycobacterium bovis with the Bovine Innate Immune Cells.

Federico Carlos Blanco,Fabiana Bigi,Mary Jackson,Elizabeth Andrea García,María Mercedes Bigi,María José Gravisaco,Mike Mcneil,Cecilia Marquez

doi:10.3389/fimmu.2021.674643

Abstract

Bovine tuberculosis is an important animal and zoonotic disease caused by Mycobacterium bovis. The innate immune response is the first line of defense against pathogens and is also crucial for the development of an efficient adaptive immune response. In this study we used an in vitro co-culture model of antigen presenting cells (APC) and autologous lymphocytes derived from peripheral blood mononuclear cells to identify the cell populations and immune mediators that participate in the development of an efficient innate response capable of controlling the intracellular replication of M. bovis. After M. bovis infection, bovine immune cell cultures displayed upregulated levels of iNOS, IL-22 and IFN-γ and the induction of the innate immune response was dependent on the presence of differentiated APC. Among the analyzed M. bovis isolates, only a live virulent M. bovis isolate induced an efficient innate immune response, which was increased upon stimulation of cell co-cultures with the M. bovis culture supernatant. Moreover, we demonstrated that an allelic variation of the early secreted protein ESAT-6 (ESAT6 T63A) expressed in the virulent strain is involved in this increased innate immune response. These results highlight the relevance of the compounds secreted by live M. bovis as well as the variability among the assessed M. bovis strains to induce an efficient innate immune response.

Highlights

Bovine tuberculosis is an important animal and zoonotic disease that causes significant financial loss worldwide and represents a public health hazard
We evaluated the expression of immune mediators in cocultures of M. bovis-infected macrophages and autologous lymphocytes
To characterize a pro-inflammatory activation pathway and relevant cell receptors, we studied the expression of Toll like receptor 2 (TLR2), Toll like receptor 4 (TLR4), Myeloid differentiation primary response protein (MyD88), dendritic cell–specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) and the mannose receptor type 1 (MRC1)

Summary

Introduction

Bovine tuberculosis (bTB) is an important animal and zoonotic disease that causes significant financial loss worldwide and represents a public health hazard. Losses due to TB are estimated to be US$ 3 billion per year, with more than 50 million cattle infected [1]. The costs of this disease are related to reduced productivity in severely affected animals, testing, slaughter of affected animals, movement controls, and trade restriction. In comparison to TB infection, which is mostly arrested at early stages with no or low bacterial replication, cattle M. bovis infections progress to more severe stages, producing acute infections with active mycobacterial replication [2]. The experimental evidence suggests that species-specific mycobacterial factors significantly contribute to the observed differences in the pathology of TB and bTB [2]

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Results

Conclusion