Interleukin-4 (IL-4) and IL-13 Signaling Pathways Do Not RegulateBorrelia burgdorferi-Induced Arthritis in Mice: IgG1 Is Not Required for Host Control of Tissue Spirochetes

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Abstract
Previous studies have suggested that interleukin-4 (IL-4) has a protective effect in host defense toBorrelia burgdorferiinfection, both in limiting the severity of arthritis and in controlling spirochete numbers in tissues, and a mapping study revealed suggestive linkage to a cluster of genes on mouse chromosome 11, including the genes for IL-4 and IL-13. In contrast, other studies have questioned the importance of IL-4. In this study the involvement of IL-4 in murine Lyme disease was examined in C57BL/6J and BALB/cJ mice with targeted disruptions in the IL-4 gene, the IL-4Rα chain gene, or both. A spectrum of arthritis severity was seen in BALB/cJ mice, and ablation of IL-4, IL-4Rα, or both had no effect on the overall severity of arthritis as determined by joint swelling and histopathology. Wild-type C57BL/6J mice exhibited mild to moderate arthritis, and ablation of IL-4 again had no effect on arthritis severity. IL-4- and IL-4Rα-deficient mice produced extremely low levels of immunoglobulin G1 (IgG1) and showed increased production of IgG2b. This shift in immunoglobulin isotype had no effect on the host's ability to control spirochete growth in either strain of mouse, as determined by PCR detection ofB. burgdorferiDNA from heart and ankle tissues. In summary, the IL-4-IL-4Rα pathway, including IL-13 signaling, neither limits arthritis severity nor is required for control of spirochete growth duringB. burgdorferiinfection of mice. Furthermore, the IgG1 isotype is not required to controlB. burgdorfericell numbers in tissues. These findings suggest the host defense againstB. burgdorferiinfection is not dependent on the Th1-Th2 paradigm of T-cell responses.