Abstract

Brucellosis is a prevalent global zoonotic infection but has far more impact in developing countries. The adipocytes are the most abundant cell type of adipose tissue and their secreted factors play an important role in several aspects of the innate and adaptive immune response. Here, we demonstrated the ability of Brucella abortus to infect and replicate in both adipocytes and its precursor cells (pre-adipocytes) derived from 3T3-L1 cell line. Additionally, infection of pre-adipocytes also inhibited adipogenesis in a mechanism independent of bacterial viability and dependent on lipidated outer membrane protein (L-Omp19). B. abortus infection was able to modulate the secretion of IL-6 and the matrix metalloproteases (MMPs) -2 and-9 in pre-adipocytes and adipocytes, and also modulated de transcription of adiponectin, leptin, and resistin in differentiated adipocytes. B. abortus-infected macrophages also modulate adipocyte differentiation involving a TNF-α dependent mechanism, thus suggesting a plausible interplay between B. abortus, adipocytes, and macrophages. In conclusion, B. abortus is able to alter adipogenesis process in adipocytes and its precursors directly after their infection, or merely their exposure to the B. abortus lipoproteins, and indirectly through soluble factors released by B. abortus-infected macrophages.

Highlights

  • Brucellosis is a prevalent global zoonotic infection but has far more impact in developing countries [1]

  • We investigate whether B. abortus can infect and survive in differentiated adipocyte and its precursors, as well as the incumbency on both adipogenesis and immune response modulation, on the inflammatory response during brucellosis

  • Adipocytes were less permissive for B. abortus growth, and the number of bacteria in adipocytes was significantly lower than that observed for pre-adipocytes (p < 0.01)

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Summary

Introduction

Brucellosis is a prevalent global zoonotic infection but has far more impact in developing countries [1]. Clinical manifestations of brucellosis are frequently associated with inflammatory responses in the organs affected [2]. Adipose tissue represents one of the largest organs and constitutes up to 25% of the mass of the body in normal weight individuals [3]. It is distributed throughout the body and is made up of different cell types that are involved in storing energy, regulating metabolism in addition to fulfilling neuroendocrine and immunological functions [3]. The resident immune cells—which include lymphocytes and macrophages— secrete multiple inflammatory mediators, again including classical cytokines and chemokines [4, 5]

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