Factors affecting the levels of protection transferred from mother to offspring following immune challenge.

INTRODUCTION: The transfer of antibodies from mother to offspring is key to protecting young animals from disease and can have a major impact on responses to infection and offspring fitness. Such maternal effects also allow young that may be exposed to disease in early life to focus resources on growth and development at this critical period of development. Maternally transferred antibodies are therefore an important source of phenotypic variation in host phenotype as well as influencing host susceptibility and tolerance to infection across generations. It has previously been assumed the transfer of antibodies is passive and invariant and reflects the level of circulating antibody in the mother at the time of transfer. However, whether females may vary in the relative amount of protection transferred to offspring has seldom been explored. RESULTS: Here we show that females differ widely in the relative amount of specific blood antibodies they transfer to the embryonic environment (range 9.2%-38.4% of their own circulating levels) in Chinese painted quail (Coturnix chinensis). Relative transfer levels were unrelated to the size of a female's own immune response. Furthermore, individual females were consistent in their transfer level, both across different stages of their immune response and when challenged with different vaccine types. The amount of antibody transferred was related to female condition, but baseline antibody responses of mothers were not. However, we found no evidence for any trade-offs between the relative amount of antibody transferred with other measures of reproductive investment. CONCLUSIONS: These results suggest that the relative amount of antibodies transferred to offspring can vary significantly and consistently between females. Levels of transfer may therefore be a separate trait open to manipulation or selection with potential consequences for offspring health and fitness in both wild and domesticated populations

Human immunodeficiency virus rebound after suppression to < 400 copies/mL during initial highly active antiretroviral therapy regimens, according to prior nucleoside experience and duration of suppression

This study evaluated 1433 human immunodeficiency virus (HIV)-infected patients starting highly active antiretroviral therapy (HAART), 409 (28%) of whom had prior nucleoside experience and achieved an HIV load of <400 copies/mL by 24 weeks of therapy. Three hundred seven patients experienced virus rebound during a total of 2773.3 person-years of follow-up. There was a higher rate of virus rebound among the patients with pre-HAART nucleoside experience (relative hazard [RH], 2.86; 95% confidence interval, 2.22-3.84; P < .0001) and a decreasing rate of virus rebound with increasing duration of virus suppression (i.e., time since achieving a virus load of <400 HIV RNA copies/mL) among both the nucleoside-experienced and naive patients (P < .0001), but the difference between the groups persisted into the third year of follow-up (P = .0007). Even patients who had experienced <2 months of nucleoside therapy before beginning HAART had an increased risk of virus rebound (RH, 1.95; P = .009). It appears that only a small period of pre-HAART nucleoside therapy is sufficient to confer a disadvantage, in terms of risk of virus rebound, that persists for several years

Seabirds and the circulation of Lyme borreliosis bacteria in the North Pacific

Seabirds act as natural reservoirs to Lyme borreliosis spirochetes and may play a significant role in the global circulation of these pathogens. While Borrelia burgdorferi sensu lato (Bbsl) has been shown to occur in ticks collected from certain locations in the North Pacific, little is known about interspecific differences in exposure within the seabird communities of this region. We examined the prevalence of anti-Bbsl antibodies in 805 individuals of nine seabird species breeding across the North Pacific. Seroprevalence varied strongly among species and locations. Murres (Uria spp.) showed the highest antibody prevalence and may play a major role in facilitating Bbsl circulation at a worldwide scale. Other species showed little or no signs of exposure, despite being present in multispecific colonies with seropositive birds. Complex dynamics may be operating in this wide scale, natural hostparasite system, possibly mediated by the host immune system and host specialization of the tick vector

Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution

Microglia have critical roles not only in neural development and homeostasis, but also in neurodegenerative and neuroinflammatory diseases of the central nervous system(1-4). These highly diverse and specialized functions may be executed by subsets of microglia that already exist in situ, or by specific subsets of microglia that develop from a homogeneous pool of cells on demand. However, little is known about the presence of spatially and temporally restricted subclasses of microglia in the central nervous system during development or disease. Here we combine massively parallel single-cell analysis, single-molecule fluorescence in situ hybridization, advanced immunohistochemistry and computational modelling to comprehensively characterize subclasses of microglia in multiple regions of the central nervous system during development and disease. Single-cell analysis of tissues of the central nervous system during homeostasis in mice revealed specific time- and region-dependent subtypes of microglia. Demyelinating and neurodegenerative diseases evoked context-dependent subtypes of microglia with distinct molecular hallmarks and diverse cellular kinetics. Corresponding clusters of microglia were also identified in healthy human brains, and the brains of patients with multiple sclerosis. Our data provide insights into the endogenous immune system of the central nervous system during development, homeostasis and disease, and may also provide new targets for the treatment of neurodegenerative and neuroinflammatory pathologies