Lack of Interleukin-6 Affects IFN-γ and TNF-α Production and Early In Vivo Control of Brucella abortus Infection

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine promptly produced in response to infections, which contributes to host defense through the stimulation of acute phase immune responses. Brucella abortus is an intracellular bacterium that causes chronic disease in humans and domestic animals and triggers a robust immune response, characterized by the production of inflammatory cytokines. However, the mechanisms of IL-6-related immune responses in the context of Brucella infections are not completely understood. In this report, we describe an increased susceptibility of IL-6 knockout (KO) mice in the early phase of Brucella infection. Furthermore, we demonstrate that IL-6 is required for interferon (IFN)-γ and tumor necrosis factor (TNF)-α induction by infected splenocytes, indicating a protective role for IL-6 against B. abortus that parallels with Th1 type of immune response. Additionally, IL-6 KO mice exhibited reduced splenomegaly during the early phase of the infection. Corroborating this result, IL-6 KO mice displayed reduced numbers of macrophages, dendritic cells, and neutrophils in the spleen and reduced myeloperoxidase activity in the liver compared to wild-type infected mice. However, we demonstrate that IL-6 is not involved in B. abortus intracellular restriction in mouse macrophages. Taken together, our findings demonstrate that IL-6 contributes to host resistance during the early phase of B. abortus infection in vivo, and suggest that its protective role maybe partially mediated by proinflammatory immune responses and immune cell recruitment.

Kinetics of Placental Infection by Different Smooth Brucella Strains in Mice

“…As in our work, trophoblastic cell lines have demonstrated their suitability for Brucella pathogenesis research [ 15 , 16 , 33 , 34 , 36 , 43 ]. This finding could be attributable to the presence of detectable concentrations of hypothetical factors of Brucella tropism, such as erythritol and aldose reductase [ 4 , 45 ].…”

“…No significative IL-12, IFN-γ, and TNF-α fluctuations were detected for B. suis bv2 and PBS control groups along pregnancy. IL-6 is considered a key mediator of proinflammatory response to LPS [ 32 , 33 , 34 ]; its levels rose significantly at 5 and 7 days PI in all Brucella infected mice vs. the PBS control group.…”

Epitope-Based Vaccine of a Brucella abortus Putative Small RNA Target Induces Protection and Less Tissue Damage in Mice

“…High levels of IL-6 were produced by the splenocytes of immunized and infected mice. It was recently shown that IL-6 is required for the induction of IFN-g and TNF-a by infected splenocytes, in addition to promoting the differentiation of CD8+ T cells, indicating a protective role for IL-6 against B. abortus that parallels the type of Th1 immunity response (109,110). Similarly, significant levels of IL-10 in immunized mice were also detected in spleen cells.…”

Galectin‐3 regulates proinflammatory cytokine function and favoursBrucella abortuschronic replication in macrophages and mice

“…BMDMs were infected in vitro with virulent B. abortus strain 2,308 or virB2 mutant strain at an MOI of 100:1 in DMEM supplemented with 10% FBS for 24 hr as previously described (Guimaraes et al, 2019). In confocal microscopy experiments, BMDMs were infected with B. abortus –GFP at an MOI of 20:1 (Guimaraes, Martins, Gomes, Cerqueira, & Oliveira, 2020).…”

“…Macrophages were plated at a density of 5 × 10 5 cells/well in 24‐well plates. BMDMs were infected with B. abortus at an MOI of 100 for 24 hr as previously described (Guimaraes et al, 2020). Cells were also stimulated with 1 μg/ml of E. coli LPS (Sigma‐Aldrich, St. Louis, MO) for 4 hr and with 20 μM nigericin sodium salt (Sigma‐Aldrich) for 30 min or stimulated with 1 μg/ml of E. coli LPS for 24 hr (Cerqueira et al, 2018).…”