Interleukin‐4 and listeriosis

Abstract

Experimental infection of mice with Listeria monocytogenes (L. monocytogenes) has served as an appropriate model for analyzing Th1-cell-driven immune responses. Generally, Th2 responses are absent and IL-4 is not detectable. Here, we describe experimental settings under which IL-4 is detectable in listeriosis. Our data suggest that IL-4 is rapidly produced after infection. This prompt IL-4 burst seems to stimulate chemokine responses and, therefore, may participate in the regulation of the early antilisterial host response. Soon thereafter, IL-4 production wanes. At least partially this seems to be caused by downregulation of IL-4-producing CD4+ NK1+ TCR alpha beta int lymphocytes by IL-12. In the absence of IFN-gamma responsiveness, IL-4 production is demonstrable during acquired immunity against L monocytogenes, and this elevated IL-4 production apparently contributes to disease exacerbation. In conclusion, the data are consistent with a detrimental role of IL-4 in listeriosis and active control of IL-4 synthesis by the antilisterial immune response. The rapid, but transient, IL-4 burst in listeriosis probably contributes to host defense without impairing development of the acquired T-cell response because of its shortness.

Induction of Interleukin-4 (IL-4) byLegionella pneumophilaInfection in BALB/c Mice and Regulation of Tumor Necrosis Factor Alpha, IL-6, and IL-1β

“…Furthermore, treating deficient mice with anti-TNF-␣ antibodies protects the animals from L. pneumophila infection. IL-4 has been shown to induce the production of MCP-1 in an L. monocytogenes infection model (12,20). This did not occur following L. pneumophila infection, as evidenced by the finding that the mobilization of MCP-1 was equivalent in both IL-4-competent and IL-4-deficient mice.…”

“…MCP-1 has been demonstrated to be induced by IL-4 in listeriosis (6,12,20). Additionally, MCP-1 has been shown to reduce lipopolysaccharide-induced mortality (47), suggesting that IL-4 could be controlling IL-1␤, TNF-␣, and IL-6 by inducing MCP-1.…”

“…However, IL-4 was detected in mice within 3 h of infection with Listeria monocytogenes (6,12,15) and Mycobacterium tuberculosis (6,7), and the transient IL-4 did not interfere with development of Th1 responses. More recently, IL-4 has been demonstrated to induce monocyte chemoattractant protein-1 (MCP-1) production during innate immunity to L. monocytogenes (6,12,20), and this induction of MCP-1 mediates the recruitment of monocytes, macrophages, and activated T cells (14). In the present study, we report that L. pneumophila infection also induces an IL-4 response along with MCP-1, IL-12, IFN-␥, TNF-␣, IL-1␤, and IL-6.…”

Enhanced Gamma Interferon Production through Activation of Vα14+Natural Killer T Cells by α-Galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis

“…Natural killer T cells (NKT cells), a subset of T cells that coexpress NK cell receptors, play important roles in various aspects of immune responses, including regulation of allergic and autoimmune diseases, prevention of tumor metastasis, and protection against bacterial and parasitic infections (3,7,12,15,18,37,42). ␣-Galactosylceramide (␣-GalCer), a synthetic glycolipid, is recognized in a specific manner by V␣14 ϩ NKT cells (12,25), which results in the production of both gamma interferon (IFN-␥) and interleukin-4 (IL-4) (4,12,25,39) and also in the apoptotic death of these cells (9,34).…”

Vaccination with Mouse Mammary Adenocarcinoma Cells Coexpressing B7-1 (CD80) and B7-2 (CD86) Discloses the Dominant Effect of B7-1 in the Induction of Antitumor Immunity

“…We can only speculate that a different balance of these cytokines influences the development of T cell subsets that are more efficient antitumor effectors than those induced by TS/A-B7-1 vaccines. Because a burst of IL-4 is required for both priming and expansion of CTLs (48,49), as well as for the development of a protective Th1 response against intracellular parasites (50,51), nonreplicating TS/A-2 cells may be more immunogenic than TS/A-1 cells due to their superiority in eliciting an initial burst of this cytokine. On the other hand, it is possible that reduced induction of IFN-␥ by TS/A-2 vaccines may also relate to their higher immunogenicity.…”