Infection of C3H mice with Borrelia burgdorferi, the causative agent of Lyme disease, reliably produces an infectious arthritis and carditis that peak around 3 weeks postinfection and then spontaneously resolve. Macrophage polarization has been suggested to drive inflammation, the clearance of bacteria, and tissue repair and resolution in a variety of infectious disease models. During Lyme disease it is clear that macrophages are capable of clearing Borrelia spirochetes and exhausted neutrophils; however, the role of macrophage phenotype in disease development or resolution has not been studied. Using classical (NOS2) and alternative (CD206) macrophage subset-specific markers, we determined the phenotype of F4/80 ؉ macrophages within the joints and heart throughout the infection time course. Within the joint, CD206؉ macrophages dominated throughout the course of infection, and NOS2؉ macrophage numbers became elevated only during the peak of inflammation. We also found dual NOS2 ؉ CD206 ؉ macrophages which increased during resolution. In contrast to findings for the ankle joints, numbers of NOS2 ؉ and CD206؉ macrophages in the heart were similar at the peak of inflammation. 5-Lipoxygenase-deficient (5-LOX ؊/؊ ) mice, which display a failure of Lyme arthritis resolution, recruited fewer F4/80 ؉ cells to the infected joints and heart, but macrophage subset populations were unchanged. These results highlight differences in the inflammatory infiltrates during Lyme arthritis and carditis and demonstrate the coexistence of multiple macrophage subsets within a single inflammatory site. Macrophages play a dynamic role in the immune system as both inflammatory and anti-inflammatory mediators. Their phenotype is highly flexible and dependent upon the cytokine stimulus of the microenvironment they infiltrate (1). They are routinely classified as proinflammatory and immunomodulatory (M1) or anti-inflammatory and remodeling (M2) macrophages, but their phenotype actually lies within a spectrum of inflammatory to anti-inflammatory polarization (2). The language within the field is currently being modified to ensure that the macrophages being studied have a clear phenotypic description, and we use the nomenclature recently suggested (3). Within the last 15 years, much work has been done to phenotypically characterize macrophage subsets. Identifying unique surface and intracellular markers, as well as understanding transcriptional regulation, has allowed the importance of specific macrophage phenotypes in infectious and autoimmune models to be uncovered.Classically activated M1 macrophages are proinflammatory cells capable of destroying pathogens, tumor cells, and various foreign compounds. Stimulation of undifferentiated macrophages with lipopolysaccharide (LPS) and gamma interferon (IFN-␥), or tumor necrosis factor alpha (TNF-␣), induces polarization to the M1 phenotype (4, 5). They can be recognized both in vitro and in vivo by the production of nitric oxide species (NOS), as well as other proinflammatory molecules, including ...

Unresolved experimental Lyme arthritis in C3H 5-lipoxygenase (5-LOX) mice is associated with impaired macrophage phagocytosis of In the present study, we further investigated the effects of the 5-LOX metabolite, leukotriene (LT)B on phagocytosis of Bone marrow-derived macrophages (BMDMs) from 5-LOX mice were defective in the uptake and killing of from the earliest stages of spirochete internalization. BMDMs from mice deficient for the LTB high-affinity receptor (BLT1) were also unable to efficiently phagocytose Addition of exogenous LTB augmented the phagocytic capability of BMDMs from both 5-LOX and BLT1 mice, suggesting that the low-affinity LTB receptor, BLT2, might be involved. Blocking BLT2 activity with the specific antagonist, LY255283, inhibited phagocytosis in LTB-stimulated BLT1 BMDMs, demonstrating a role for BLT2. However, the lack of a phagocytic defect in BLT2 BMDMs suggested that this was a compensatory effect. In contrast, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, a natural BLT2-specific high-affinity ligand, and resolvin E1, a BLT1 agonist, were both unable to boost phagocytosis in BMDMs from either 5-LOX or BLT1 mice, suggesting a specific role for LTB in mediating phagocytosis in murine macrophages. This study demonstrates that LTB promotes macrophage phagocytosis of bacteria via BLT1, and that BLT2 can fulfill this role in the absence of BLT1.

Eggplant fruits are known to contain different classes of phenolic phytochemicals (flavonols, phenolic acids, and anthocyanins) that can exert beneficial effects on human health. This study developed methods for the qualitative and quantitative composition analysis of phenolic compounds in the skin of eggplant fruits harvested following conventional and certified organic farming conditions. Eggplant skin was extracted using aqueous methanol prior to phenolic profiling with UHPLC-ESI-MS-MS. Eggplant skin extracts yielded a profile of 16 phenolic acids, 4 anthocyanins, and 11 flavonols, the first report of quercetin-3-diglucoside, myricetin-3-neohesperidoside, myricetin-3-galactoside, kaempferol-3,7-diglucoside, kaempferol-diglucoside and quercetin-3-rhamnoside. Polyphenolic extracts from all sources potently delayed the cupric ion-mediated lag-time for LDL lipid oxidation and protected Apo-B100 proteins against oxidative modification. Organic growing environment positively influences eggplant skin extract phenolic profile but not antioxidant capacity. In conclusion, eggplant skin has a robust profile of phenolic phytochemicals with excellent antioxidant properties.

Yersinia pestis causes bubonic, pneumonic, and septicemic plague, diseases that are rapidly lethal to most mammals, including humans. Plague develops as a consequence of bacterial neutralization of the host's innate immune response, which permits uncontrolled growth and causes the systemic hyperactivation of the inflammatory response. We previously found that host type I interferon (IFN) signaling is induced during Y. pestis infection and contributes to neutrophil depletion and disease. In this work, we show that type I IFN expression is derived from the recognition of intracellular Y. pestis by host Toll-like receptor 7 (TLR7). Type I IFN expression proceeded independent of myeloid differentiation factor 88 (MyD88), which is the only known signaling adaptor for TLR7, suggesting that a noncanonical mechanism occurs in Y. pestis-infected macrophages. In the murine plague model, TLR7 was a significant contributor to the expression of serum IFN-β, whereas MyD88 was not. Furthermore, like the type I IFN response, TLR7 contributed to the lethality of septicemic plague and was associated with the suppression of neutrophilic inflammation. In contrast, TLR7 was important for defense against disease in the lungs. Together, these data demonstrate that an atypical TLR7 signaling pathway contributes to type I IFN expression during Y. pestis infection and suggest that the TLR7-driven type I IFN response plays an important role in determining the outcome of plague.