Access to voluntary running wheel exercise: Prevention of anxiety-like behavior in chronically stressed rats, but potentiation of ethanol intake/preference.

The current study tested the effect of voluntary running on future anxiety-like behavior, physiological response to stress, and ethanol intake/preference, while including a chronically stressed group and healthy group housed conspecifics. When given concurrently, voluntary running reduces ethanol intake, though it is unknown what effect voluntary running will have on anxiety-like behavior, corticosterone response to stress, and ethanol intake/preference when exercise is allowed only prior to ethanol access. Adolescent male Long Evans rats arrived in the lab at postnatal day (PND) 21. At PND 27, rats were either socially isolated (SI; n = 1/cage) or group housed (GH; n = 4/cage). Half of each group was allowed access to a running wheel for 30 min for 24 days from PND 35-66, and half of each group was not allowed access to a running wheel. After the housing/running procedure, we tested anxiety-like behavior using the elevated plus maze and stress responsivity by measuring corticosterone (CORT) levels before and after a swim stressor; then, rats were allowed intermittent access to ethanol in two-bottle choice design for four weeks. In accord with our hypothesis, running reduced anxiety-like behavior in SI runners compared to non-runners. Swim stress increased CORT levels but there was no difference in the response among groups. In regard to ethanol intake and preference, running (irrespective of housing group) increased intake at the 30 min time point and preference at the 24 h time point. Altogether, these data show that access to voluntary exercise was successful in reducing anxiety-like behavior, but withdrawal of exercise access appeared to enhance ethanol intake/preference. We suggest that these data reflect hedonic substitution.

Comparing and refining karst disturbance index methods through application in an island karst setting.

The interconnected nature of surface and subsurface karst environments allows easy disturbance to their aquifers and specialized ecosystems from anthropogenic impacts. The karst disturbance index is a holistic tool used to measure disturbance to karst environments and has been applied and refined through studies in Florida and Italy, among others. Through these applications, the karst disturbance index has evolved into two commonly used methods of application; yet, the karst disturbance index is still susceptible to evaluation and modification for application in other areas around the world. The geographically isolated and highly vulnerable municipality of Arecibo, Puerto Rico's karst area provides an opportunity to test the usefulness and validity of the karst disturbance index in an island setting and to compare and further refine the application of the original and modified methods. This study found the both methods of karst disturbance index application resulted in high disturbance scores (Original Method 0.54 and Modified Method 0.69, respectively) and uncovered multiple considerations for the improvement of the karst disturbance index. An evaluation of multiple methods together in an island setting also resulted in the need for adding additional indicators, including Mogote Removal and Coastal Karst. Collectively, the results provide a holistic approach to using the karst disturbance index in an island karst setting and suggest a modified method by which scaling and weighting may compensate for the difference between the original and modified method scores and allow interested stakeholders to evaluate disturbance regardless of his or her level of expertise.

The onset of CD8+-T-cell contraction is influenced by the peak of Listeria monocytogenes infection and antigen display.

The CD8+-T-cell response to infection with Listeria monocytogenes consists of expansion, contraction, and memory phases. The transition between expansion and contraction is reported to occur on different days postinfection with virulent (8 to 9 days) and attenuated (DeltaactA) (7 days) L. monocytogenes strains. We hypothesized that differences in the infectious courses, and therefore antigen (Ag) display, determine the precise time of the expansion/contraction transition in response to these infections. To test this, we infected BALB/c mice with 0.1 50% lethal dose of DeltaactA or virulent L. monocytogenes and measured bacterial numbers, Ag display, and Ag-specific CD8+-T-cell responses on various days after infection. We found that bacterial numbers and Ag display peaked between 12 and 36 h and between 36 and 60 h after infection with DeltaactA and virulent L. monocytogenes strains, respectively. Infection with DeltaactA L. monocytogenes resulted in a sharp peak in the Ag-specific CD8+-T-cell response on day 7, while infection with virulent L. monocytogenes yielded a prolonged peak with equivalent numbers of Ag-specific CD8+ T cells on days 6, 7, and 8 after infection. Truncating virulent infection with antibiotics on day 1 or 2 after infection resulted in a shift in the expansion/contraction transition from day 8 to day 7 after infection. However, antibiotic treatment beginning on day 3, after the peak of virulent L. monocytogenes infection and Ag display, had no effect upon the magnitude or timing of the CD8+-T-cell response. These results demonstrate a direct relationship between the course of infection and Ag display and that the timing of these events is important in shaping the T-cell response to infection.

CD8+ T cell contraction is controlled by early inflammation.

Pathogen-specific CD8(+) T cells expand in number after infection and then their numbers invariably contract by 90-95%, leaving a stable memory cell pool. The chief features of this response are programmed early after infection; however, the factors regulating contraction are mostly undefined. Here we show that antibiotic treatment before Listeria monocytogenes infection induced numbers of protective memory CD8(+) T cells similar to those in control infected mice, by a pathway without contraction. The absence of contraction correlated with decreased early inflammation and interferon-gamma production and an increased fraction of CD8(+) T cells expressing the interleukin 7 receptor at the peak of the response. Thus, contraction is controlled by early inflammation but is not essential for the generation of protective memory CD8(+) T cells after infection.

MHC class Ia-restricted memory T cells inhibit expansion of a nonprotective MHC class Ib (H2-M3)-restricted memory response.

Listeria monocytogenes infection generates major histocompatibility complex (MHC) class Ia-restricted and MHC class Ib-(H2-M3)-restricted effector and memory CD8+ T cells. However, only MHC class Ia-restricted memory cells expand after rechallenge, and it is unknown if MHC class Ib-restricted memory CD8+ T cells generated by vaccination are protective. We show here that H2-M3-restricted memory CD8+ T cells were capable of secondary expansion but, in contrast to primary H2-M3-restricted effector cells, failed to provide protective immunity. In lm-immune mice, MHC class Ia-restricted memory CD8+ T cells prevented the expansion of H2-M3-restricted memory T cell populations by limiting dendritic cell antigen presentation. Thus, protective immunity by H2-M3-restricted T cells is limited to primary infection, indicating that memory MHC class Ia-restricted T cells prevent nonessential immune responses during secondary infection.

Cutting edge: Mycobacterium tuberculosis blocks Ca2+ signaling and phagosome maturation in human macrophages via specific inhibition of sphingosine kinase.

One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), and three million people die of tuberculosis each year. Following its ingestion by macrophages (MPs), Mtb inhibits the maturation of its phagosome, preventing progression to a bactericidal phagolysosome. Phagocytosis of Mtb is uncoupled from the elevation in MP cytosolic Ca(2+) that normally accompanies microbial ingestion, resulting in inhibition of phagosome-lysosome fusion and increased intracellular viability. This study demonstrates that the mechanism responsible for this failure of Ca(2+)-dependent phagosome maturation involves mycobacterial inhibition of MP sphingosine kinase. Thus, inhibition of sphingosine kinase directly contributes to survival of Mtb within human MPs and represents a novel molecular mechanism of pathogenesis.

Programmed contraction of CD8(+) T cells after infection.

The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of antigen-specific CD8(+) T cell expansion and the ensuing contraction to a stable number of memory cells. We show that CD8(+) T cell expansion after Listeria monocytogenes infection was primarily dependent on the initial infection dose or amount of antigen displayed, and was also influenced by the rate of pathogen clearance. However, the onset and kinetics of CD8(+) T cell contraction after L. monocytogenes and lymphocytic choriomeningitis virus infections were independent of the magnitude of expansion, dose and duration of infection or amount of antigen displayed. Thus, major features of antigen-specific CD8(+) T cell homeostasis, including the contraction phase of an immune response, may be programmed early after infection.