Interleukin-4 (IL-4) and IL-13 signaling pathways do not regulate Borreliaburgdorferi-induced arthritis in mice: IgG1 is not required for host control of tissue spirochetes

Previous studies have suggested that interleukin-4 (IL-4) has a protective effect in host defense to Borrelia burgdorferi infection, 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 m ouse chromosome Il, including the genes for IL-4 and IL-13. In contrast, ot her studies have questioned the importance of IL-4, In this study the invol vement 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-4R alpha chain gene , or both. A spectrum of arthritis severity was seen in BALB/cJ mice, and a blation of IL-4, IL-4R alpha, or both had no effect on the overall severity of arthritis as determined by joint swelling and histopathology, Wild-type C57B/6J mice exhibited mild to moderate arthritis, and ablation of IL-4 ag ain had no effect on arthritis severity. IL-4- and IL-4R alpha-deficient mi ce produced extremely low levels of immunoglobulin G1 (IgG1) and showed inc reased production of IgG2b. This shift in immunoglobulin isotype had no eff ect on the host's ability to control spirochete growth in either strain of mouse, as determined by PCR detection of B. burgdorferi DNA from heart and ankle tissues. In summary, the IL-4-IL-4R alpha pathway, including IL-13 si gnaling, neither limits arthritis severity nor is required for control of s pirochete growth during B, burgdorferi infection of mice. Furthermore, the IgG1 isotype is not required to control B, burgdorferi cell numbers in tiss ues, These findings suggest the host defense against B, burgdorferi infecti on is not dependent on the Th1-Th2. paradigm of T-cell responses.