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.
Highlights
Interleukin-6 (IL-6) is an immunoregulatory cytokine with a broad effect on cells of the immune system [1], and high levels of IL-6 are detected during tissue damage, microbial infection, and several other inflammatory conditions [2,3]
2C) while IL-6 KO macrophages stimulated with LPS showed no alterations in IL-10 secretion when secretion compared to wild-type cells (Figure 2D) in all analyzed conditions, including LPS. Stimulation, and these results were not related to Brucella infection levels. These results show that tumor necrosis factor (TNF)-α production is reduced in macrophages in the absence of IL-6, while IL-10 is mildly altered only with lower bacterial loads, and IL-12 is not affected by IL-6, indicating that IL-6 has a role in regulating TNF-α secretion during B. abortus infection
IL-6 has emerged as a key cytokine during bacterial infections, with complex effects on cells of IL-6 has emerged a key cytokine during bacterial infections, with complex[1,30]
Summary
Interleukin-6 (IL-6) is an immunoregulatory cytokine with a broad effect on cells of the immune system [1], and high levels of IL-6 are detected during tissue damage, microbial infection, and several other inflammatory conditions [2,3]. Gram-negative bacteria induce increased plasma levels of IL-6 during inflammation, and IL-6 expression has been proposed as a critical activator of protective immunity [4,5,6]. Several studies have shown that IL-6 acts as a powerful inflammatory cytokine that is essential for immune responses in distinct scenarios [7,8,9]. IL-6 is crucial for inducing an acute-phase inflammatory response against Listeria monocytogenes [10] and for the production of interferon-gamma (IFN-γ) during Chlamydia trachomatis [11] and Mycobacterium tuberculosis infections [6,12]. IL-6 is required for the production of tumor necrosis factor (TNF-α) during M. tuberculosis infection [6].
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