**1. Introduction**

*Brucella* spp. are Gram-negative intracellular bacteria that infect domestic and natural animals and produce an incapacitating chronic disease when transmitted to humans. In many countries, brucellosis remains endemic. The most frequent clinical characteristics are hepatomegaly, splenomegaly and peripheral lymphadenopathy, revealing the preference of *Brucella* for the reticuloendothelial system [1,2].

As a frequent niche of infections, the liver provides a tolerogenic environment. Such immunotolerant capacity is based on the presence of a resident immune cell repertoire in constant stimulation and the hepatic blood source that spread a unique growth factor and cytokine milieu [3].

However, the immune system of the liver is capable of inducing a prompt-response to tumor cells and pathogenic microorganisms [4]. Thus, the majority of the microorganisms that arrive in the liver are eradicated. Nonetheless, even though these several mechanisms can remove infectious agents, *Brucella* spp. can escape the immune response and persist in the liver. Accordingly, in humans infected with *Brucella*, the liver is frequently implicated, with a frequency between 5% to 52% or more [5]. Liver

biopsies from *Brucella abortus*-infected patients revealed the presence of granulomas with single of multiple localizations in portal and parenchymal tissue, inflammatory infiltrations, and parenchymal necrosis [6,7].

Among the non-parenchymal cells, hepatic stellate cells (HSCs) are placed among hepatocyte and small blood vessels. They are characterized by their contents of intracellular lipid droplets and protuberances that spread nearby the blood vessels. During liver injury, HSCs are activated and realize collagen with the development of scar tissue, producing chronic fibrosis or cirrhosis [8]. Furthermore, they also have a role in liver fibrosis to heal restore inflammatory injury.

During *B. abortus* infection, the protagonism of HSCs during the generation of fibrosis has recently been revealed [9]. Besides their function during liver damage through the production of fibrosis, HSCs cans also participate as local antigen-presenting cells (APCs). HSCs express MHC class I and II molecules, as well as co-stimulatory molecules such as CD40 and CD80 [10]. Accordingly, HSCs can interact with CD4+ T cells to induce effector responses [11]. In addition, HSCs direct naïve CD4+ T-cell activation to Treg differentiation in the presence of Dendritic cells (DC) [12]. Thus, the main role of HSCs is the ability to induce a tolerogenic liver milieu that can favor the chronicity of *B. abortus* infection.

Nucleated cells express MHC class I molecules, but MHC class II molecule expression is restricted for cell types such as dendritic cells, macrophages and B lymphocytes. MHC class II expression is regulated in part by the class II transactivator protein (CIITA) at the transcription level. The α- and β-chains of newly synthesized class II molecules are associated with the invariant change (Ii), giving rise to immature MHC-II. These molecules reach the cell surface, then recycle to the endosomal/lysosomal compartment, named MIIC. In this compartment, cathepsin S is one of the proteases responsible in Ii processing to Class II-associated invariant chain peptide (CLIP) in human antigen-presenting cells. Ii removal is an important step for the adequate export of the peptide-loaded class II molecule to the cell surface. Activation of HSCs by several agonists such as bacterial lipopolysaccharide (LPS) and IFN-γ drive the increase of MHC class II expression and co-stimulatory molecules [11]. Immune responses to liver pathogens need to consider the possibility that unconventional Antigen presenting cells (APC) play an important function, and may account for the miscarriage of effective immunity. Thus, the aim of this study is to characterize the induction of surface MHC-I and -II expression during *B. abortus* infection.
