Borrelia burgdorferi, the causative agent of Lyme disease, undergoes rapid adaptive gene expression in response to environmental signals encountered during different stages of its life cycle in the arthropod vector or the mammalian host. Among all the plasmid-encoded genes of B. burgdorferi, several linear plasmid 54 (lp54)-encoded open reading frames (ORFs) exhibit the greatest differential expression in response to mammalian host-specific temperature, pH, and other uncharacterized signals. These ORFs include members of the paralogous gene family 54 (pgf 54), such as BBA64, BBA65, and BBA66, present on lp54. In an attempt to correlate transcriptional up-regulation of these pgf 54 members to their role in infectivity, we inactivated BBA64 and characterized the phenotype of this mutant both in vitro and in vivo. There were no major differences in the protein profiles between the BBA64 mutant and the control strains, while immunoblot analysis indicated that inactivation of BBA64 resulted in increased levels of BBA65. Moreover, there was no significant difference in the ability of the BBA64 mutant to infect C3H/HeN mice compared to that of its parental or complemented control strains as determined by culturing of viable spirochetes from infected tissues. However, enumeration of spirochetes using quantitative real-time PCR revealed tissue-specific differences, suggesting a minimal role for BBA64 in the survival of B. burgdorferi in select tissues. Infectivity analysis of the BBA64 mutant suggests that B. burgdorferi may utilize multiple determinants to establish infection in mammalian hosts.Lyme disease is the most prevalent arthropod-borne infection in the United States and remains a significant public health issue in certain geographic loci (3,46). It is a multiphasic disorder with clinical symptoms involving the cutaneous, musculoskeletal, cardiovascular, and nervous systems (62). Borrelia burgdorferi, the causative agent of Lyme disease, is transmitted to several vertebrate hosts, including humans, by the bite of infected Ixodes ticks. When ticks consume a blood meal from mammalian hosts, there is a rapid alteration of gene expression in B. burgdorferi, facilitating adaptation of the spirochetes to the highly disparate environmental conditions that exist between the tick vector and the vertebrate host (4, 9, 10, 15, 29, 30-32, 44, 53, 57-59, 63, 67). This adaptive gene expression may aid in the efficient trafficking of the spirochetes from the tick vector to the mammalian host and subsequently facilitate dissemination and colonization of various host tissues (16,22).Whole-genome transcriptional analyses using B. burgdorferi, propagated under in vitro growth conditions that mimic either the tick vector or mammalian host environment, have revealed preferential expression of plasmid-encoded genes (4,44,53,66). Among the several linear and circular plasmids present in B. burgdorferi, linear plasmid 54 (lp54) encodes the largest number of open reading frames (ORFs) that exhibit differential gene expression in respon...

Immune senescence in the elderly results in decreased immunity with a concomitant increase in susceptibility to infection and diminished efficacy of vaccination. Nonhuman primate (NHP) models have proven critical for testing of vaccines and therapeutics in the general population, but a model using old animals has not been established. Towards that end, immunity to LcrV, a protective antigen from Yersinia pestis, was tested in young and old baboons. Surprisingly, there was no age-associated loss in immune competence; LcrV elicited high-titer, protective antibody responses in the older individuals. The primary responses in the younger baboons were lower, but they did show boosting upon secondary immunization to the levels achieved in the old animals. The LcrV antigen was also tested in mice and, as expected, age-associated loss of immunity was seen; older animals responded with lower titer antibodies and as a result, were more susceptible to Yersinia challenge. Thus, although age-related loss in immune function has been observed in humans, rodents and some nonhuman primates, baboons appear to be unusual; they age without losing immune competence.

dMucosal tissues are the primary route of transmission for most respiratory and sexually transmitted diseases, including human immunodeficiency virus (HIV). There is epidemiological evidence that genital mucosal inflammation leads to enhanced HIV type 1 (HIV-1) transmission. The objective of this study was to assess the influence of periodontal inflammation on oral HIV transmission using a nonhuman primate model of teeth ligature-induced periodontitis. Simian immunodeficiency virus (SIV) was nontraumatically applied to the gingiva after moderate gingivitis was identified through clinical and immunologic analyses (presence of inflammatory cytokines). Overall oral SIV infection rates were similar in the gingivitis-induced and control groups (5 infections following 12 SIV administrations for each), although more macaques were infected with multiple viral variants in the gingivitis group. SIV infection also affected the levels of antiviral and inflammatory cytokines in the gingival crevicular fluid, and a synergistic effect was observed, with alpha interferon and interferon-inducible protein 10 undergoing significant elevations following SIV infection in macaques with gingivitis compared to controls. These increases in antiviral and inflammatory immune modulators in the SIV-infected gingivitis macaques could also be observed in blood plasma, although the effects at both compartments were generally restricted to the acute phase of the infection. In conclusion, while moderate gingivitis was not associated with increased susceptibility to oral SIV infection, it resulted in elevated levels of cytokines in the oral mucosa and plasma of the SIV-infected macaques. These findings suggest a synergy between mucosal inflammation and SIV infection, creating an immune milieu that impacts the early stages of the SIV infection with potential implications for long-term pathogenesis.