Abstract
Lyme arthritis, caused by the spirochete Borrelia burgdorferi, can be recurrent or prolonged, whereas Lyme carditis is mostly nonrecurring. A prominent difference between arthritis and carditis is the differential representation of phagocytes in these lesions: polymorphonuclear leukocytes (PMN) are more prevalent in the joint, and macrophages predominate in the heart lesion. We have previously shown differential efficiency of B. burgdorferi clearance by PMN and macrophages, and we now investigate whether these functional differences at the cellular level may contribute to the observed differences in organ-specific pathogenesis. When we infected mice lacking the neutrophil chemokine receptor (CXCR2(-/-) mice) with spirochetes, we detected fewer PMN in joints and less-severe arthritis. Here we have investigated the effects of the absence of the macrophage chemokine receptor CCR2 on the development and resolution of Lyme carditis in resistant (C57BL/6J [B6]) and sensitive (C3H/HeJ [C3H]) strains of mice. In B6 CCR2(-/-) mice, although inflammation in hearts is mild, we detected an increased burden of B. burgdorferi compared to that in wild-type (WT) mice, suggesting reduced clearance in the absence of macrophages. In contrast, C3H CCR2(-/-) mice have severe inflammation but a decreased B. burgdorferi burden compared to that in WT C3H mice both at peak disease and during resolution. Histopathologic examination of infected hearts revealed that infected C3H CCR2(-/-) animals have an increased presence of PMN, suggesting compensatory mechanisms of B. burgdorferi clearance in the hearts of infected C3H CCR2(-/-) mice. The more efficient clearance of B. burgdorferi from hearts by CCR2(-/-) versus WT C3H mice suggests a natural defect in the recruitment or function of macrophages in C3H mice, which may contribute to the sensitivity of this strain to B. burgdorferi infection.
Highlights
Lyme disease is caused by the spirochete Borrelia burgdorferi and is characterized by the hallmark rash erythema migrans and subsequent inflammatory processes that include arthritis, carditis, and neurological symptoms [28]
We have examined carditis in mice deficient in the CCR2 type chemokine receptor (CCR2Ϫ/Ϫ mice) in both a Borreliaresistant (B6) and a Borrelia-sensitive (C3H) mouse background
We have previously shown for B. burgdorferi infection of CXCR2Ϫ/Ϫ mice that polymorphonuclear leukocytes (PMN) do not enter the joint and arthritis development is attenuated [8]
Summary
Lyme disease is caused by the spirochete Borrelia burgdorferi and is characterized by the hallmark rash erythema migrans and subsequent inflammatory processes that include arthritis, carditis, and neurological symptoms [28]. We have shown that in vitro, PMN kill B. burgdorferi efficiently only in the presence of specific antibodies and use a large array of nonoxidative products that are released from their granules [26, 29]. In contrast to PMN, macrophages kill spirochetes very efficiently, and largely internally, in the presence or absence of antibody, with little debris that could damage surrounding tissue [29,30,31,32,33]. These functional differences at the cellular level may determine the ultimate clinical outcome of Lyme disease in host organs. Deficiency in CCR2, a monocyte chemokine receptor, had no effect on arthritis, as might be expected, since macrophages constitute a smaller proportion of the inflammatory infiltrate in B. burgdorferi-infected joints [8]
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