Borrelia burgdorferi lipoproteins activate inflammatory cells through Toll-like receptor 2 (TLR2), suggesting that TLR2 could play a pivotal role in the host response to B. burgdorferi. TLR2 does play a critical role in host defense, as infected TLR2−/− mice harbored up to 100-fold more spirochetes in tissues than did TLR2+/+ littermates. Spirochetes persisted at extremely elevated levels in TLR2-deficient mice for at least 8 wk following infection. Infected TLR2−/− mice developed normal Borrelia-specific Ab responses, as measured by quantity of Borrelia-specific Ig isotypes, the kinetics of class switching to IgG, and the complexity of the Ags recognized. These findings indicate that the failure to control spirochete levels in tissues is not due to an impaired acquired immune response. While macrophages from TLR2−/− mice were not responsive to lipoproteins, they did respond to nonlipoprotein components of sonicated spirochetes. These TLR2-independent responses could play a role during the inflammatory response to B. burgdorferi, as infected TLR2−/− mice developed greater ankle swelling than wild-type littermates. Thus, while TLR2-dependent signaling pathways play a major role in the innate host defense to B. burgdorferi, both inflammatory responses and the development of the acquired humoral response can occur in the absence of TLR2.

Scatterer properties like the average effective scatterer diameter and acoustic concentration were determined in vivo using a quantitative ultrasound (QUS) technique from two tumor phenotypes grown in animal models. These tumor models included spontaneously occurring mammary fibroadenomas in rats and transplanted 4T1 mammary carcinomas in mice. The scatterer properties of average scatterer diameter and acoustic concentration were estimated using a Gaussian form factor from the backscattered ultrasound measured from both types of tumors. QUS images of the tumors were constructed utilizing estimated scatterer properties from regions in the tumors. The QUS images showed a clear distinction between the two types of tumors and a statistically significant difference existed between their estimated scatterer properties. The average scatterer diameter and acoustic concentration for the mammary fibroadenomas were estimated to be 105 +/- 25 microm and -15.6 +/- 5 dB(mm(-3)), respectively. The average scatterer diameter and acoustic concentration for the carcinomas was estimated to be 28 +/- 4.6 microm and 10.6 +/- 6.9 dB(mm(-3)), respectively. The distinctions in the scattering properties are clearly seen in the QUS images of the tumors and indicate that QUS imaging can be useful in differentiating between different types of mammary tumors.

To assess the contribution of TLR signaling in the host response to Borrelia burgdorferi, mice deficient in the common TLR adaptor protein, myeloid differentiation factor 88 (MyD88), were infected with B. burgdorferi. MyD88-deficient mice harbored extremely high levels of B. burgdorferi in tissues when compared with wild-type littermates and greater amounts of spirochetes in tissues than TLR2-deficient mice. These findings suggest that, in addition to TLR2, other MyD88-dependent pathways play a significant role in the host defense to B. burgdorferi. MyD88−/− mice maintained the ability to produce Abs directed against B. burgdorferi. Partial clearance of spirochetes was evident in long term infection studies and immune sera from MyD88-deficient mice were able to protect naive mice from infection with B. burgdorferi. Thus, the acquired immune response appeared to be functional in MyD88−/− mice, and the inability to control spirochete numbers was due to a failure of cells involved in innate defenses. Although macrophages from MyD88−/− mice responded poorly to Borrelia sonicate in vitro, MyD88−/− mice still developed an inflammatory arthritis after infection with B. burgdorferi characterized by an influx of neutrophils and mononuclear cells. The findings presented here point to a dichotomy between the recruitment of inflammatory cells to tissue and an inability of these cells to kill localized spirochetes.