BackgroundRelapsing fever spirochetes are global yet neglected pathogens causing recurrent febrile episodes, chills, nausea, vomiting, and pregnancy complications. Given these nonspecific clinical manifestations, improving diagnostic assays for relapsing fever spirochetes will allow for identification of endemic foci and expedite proper treatment. Previously, an antigen designated the Borrelia immunogenic protein A (BipA) was identified in the North American species Borrelia hermsii. Thus far, BipA appears unique to relapsing fever spirochetes. The antigen remains unidentified outside of these pathogens, while interspecies amino acid identity for BipA in relapsing fever spirochetes is only 24–36%. The current study investigated the immunogenicity of BipA in Borrelia turicatae, a species distributed in the southern United States and Latin America.Methodology/Principal Findings bipA was amplified from six isolates of Borrelia turicatae, and sequence analysis demonstrated that the gene is conserved among isolates. A tick transmission system was developed for B. turicatae in mice and a canine, two likely vertebrate hosts, which enabled the evaluation of serological responses against recombinant BipA (rBipA). These studies indicated that BipA is antigenic in both animal systems after infection by tick bite, yet serum antibodies failed to bind to B. hermsii rBipA at a detectable level. Moreover, mice continued to generate an antibody response against BipA one year after the initial infection, further demonstrating the protein's potential toward identifying endemic foci for B. turicatae.Conclusions/SignificanceThese initial studies support the hypothesis that BipA is a spirochete antigen unique to a relapsing fever Borrelia species, and could be used to improve efforts for identifying B. turicatae endemic regions.

Prolonged phenylbutazone administration caused hypoalbuminemia, neutropenia, changes in RDC arterial blood flow, and changes in VFA production. Veterinarians should monitor serum albumin concentrations and neutrophil counts and be cautious when making dosing recommendations for phenylbutazone treatment of horses.

Toll-like receptors (TLRs) 7 and 9 recognize nucleic acid determinants from viruses and bacteria and elicit the production of type I interferons and proinflammatory cytokines. TLR7 and TLR9 are similar regarding localization and signal transduction mechanisms. However, stimulation of these receptors has differing effects in modulating viral pathogenesis and in direct toxicity in the central nervous system (CNS). In the present study, we examined the potential of the TLR7 agonist imiquimod and the TLR9 agonist cytosine-phosphateguanosine oligodeoxynucleotide (CpG-ODN) to induce neuroinflammation after intracerebroventricular inoculation. CpG-ODN induced a more robust inflammatory response than did imiquimod after inoculation into the CNS, with higher levels of several proinflammatory cytokines and chemokines. The increase in cytokines and chemokines correlated with breakdown of the bloodcerebrospinal fluid barrier and recruitment of peripheral cells to the CNS in CpG-ODN-inoculated mice. In contrast, TLR7 agonists induced a strong interferon ␤ response in the CNS but only low levels of other cytokines. The difference in response to these agonists was not due to differences in distribution or longevity of the agonists but rather was correlated with cytokine production by choroid plexus cells. These results indicate that despite the high similarity of TLR7 and TLR9 in binding nucleic acids and inducing similar downstream signaling, the neuroinflammation response induced by these receptors differs dramatically due, at least in part, to activation of cells in the choroid plexus.

Rickettsia parkeri Luckman (Rickettsiales: Rickettsiaceae), a member of the spotted fever group of Rickettsia, is the tick-borne causative agent of a newly recognized, eschar-associated rickettsiosis. Because of its relatively recent designation as a pathogen, few studies have examined the pathogenesis of transmission of R. parkeri to the vertebrate host. To further elucidate the role of tick feeding in rickettsial infection of vertebrates, nymphal Amblyomma maculatum Koch (Acari: Ixodidae) were fed on C3H/HeJ mice intradermally inoculated with R. parkeri (Portsmouth strain). The ticks were allowed to feed to repletion, at which time samples were taken for histopathology, immunohistochemistry (IHC), quantitative polymerase chain reaction (qPCR) for rickettsial quantification, and reverse transcriptase polymerase chain reaction(RT-PCR)for expression of Itgax, Mcp1, and Il1β. The group of mice that received intradermal inoculation of R. parkeri with tick feeding displayed significant increases in rickettsial load and IHC staining, but not in cytokine expression, when compared with the group of mice that received intradermal inoculation of R. parkeri without tick feeding. Tick feeding alone was associated with histopathologic changes in the skin, but these changes, and particularly vascular pathology, were more pronounced in the skin of mice inoculated previously with R. parkeri and followed by tick feeding. The marked differences in IHC staining and qPCR for the R. parkeri with tick feeding group strongly suggest an important role for tick feeding in the early establishment of rickettsial infection in the skin.

In vitro and ex vivo results showed that PLGA and Chi/PLGA nanoparticles were efficiently taken up by the GI tract and could be optimized to deliver α-tocopherol to the intestine and improve its bioavailability.