Acute Brucella melitensis M16 infection model in mice treated with tumor necrosis factor-alpha inhibitors

Abstract

Introduction: There is limited data in the literature about brucellosis related to an intracellular pathogen and anti-tumor necrosis factor alpha (anti-TNFα) medication. The aim of this study was to evaluate acute Brucella infections in mice receiving anti-TNFα drug treatment. Methodology: Anti-TNFα drugs were injected in mice on the first and fifth days of the study, after which the mice were infected with B. melitensis M16 strain. Mice were sacrificed on the fourteenth day after infection. Bacterial loads in the liver and spleen were defined, and histopathological changes were evaluated. Results: Neither the liver nor the spleen showed an increased bacterial load in all anti-TNFα drug groups when compared to a non-treated, infected group. The most significant histopathological findings were neutrophil infiltrations in the red pulp of the spleen and apoptotic cells with hepatocellular pleomorphism in the liver. There was no significant difference among the groups in terms of previously reported histopathological findings, such as extramedullary hematopoiesis and granuloma formation. Conclusions: There were no differences in hepatic and splenic bacterial load and granuloma formation, which indicate worsening of the acute Brucella infection in mice; in other words, anti-TNFα treatment did not exacerbate the acute Brucella spp. infection in mice.

Brucella Downregulates Tumor Necrosis Factor-α to Promote Intracellular Survival via Omp25 Regulation of Different MicroRNAs in Porcine and Murine Macrophages

“…Thus, the activity of macrophages is very critical for the resistance of Brucella infection ( 5 ). As a crucial cytokine, tumor necrosis factor (TNF)-α can activate macrophages and protect human and animals from persistent Brucella infection ( 6 , 7 ). However, the production of TNF-α is severely impaired in patients and domestic animals infected with Brucella species ( 8 – 10 ).…”

“…Compared to their parental wild-type (WT) strains, Omp25-deficient Brucella melitensis, Brucella abortus, or Brucella ovis mutants show an attenuated virulence in the infected murine model and ruminant hosts ( 14 – 16 ). WT B. melitensis or Brucella suis infection exhibits a compromised ability to induce TNF-α ( 6 , 17 ), yet Omp25-deficient B. suis shows an enhanced ability to induce TNF-α in human macrophages. These data suggest Omp25 plays an important role in inhibiting TNF-α production, yet the molecular mechanism of how Brucella Omp25 inhibits TNF-α production are unclear and remain to be determined.…”

The In Vitro and In Vivo Effect of Lipoxygenase Pathway Inhibitors Nordihydroguaiaretic Acid and Its Derivative Tetra-O-methyl Nordihydroguaiaretic Acid againstBrucella abortus544

“…These two cytokines were also observed to be higher in ZIL-treated mice suggesting the role of these cytokines in the control of Brucella dissemination in the mice. TNF-α plays a critical role in the activation of macrophages and is required for an effective clearance of Brucella infection while MCP-1 is reported to be important for antiviral immune responses and observed to play a role in the control of B. abortus infection [ 30 - 32 ]. Mice treated with DPI displayed increased serum level of IL-12 at 7 d post-infection suggesting its positive role in the proliferation of Brucella in the spleens of these mice.…”