Immune Alterations Induced by Social Defeat Do Not Alter the Course of an On-Going BCG Infection in Mice

Abstract

The timing for applying stressor and primary immunization is known to influence the nature of the immune alterations induced by stress. The aim of the present study was to investigate the consequences of a stress occurring several days after the beginning of a primary infection on the host resistance. For this purpose, we investigated the effects of repeated social defeat on the immune response of mice infected with BCG 11 days before. In vitro production of cytokines in response to LPS or tuberculin, and the sensitivity of spleen cells to corticosterone were assessed 8 days after the end of the stress. Bacterial growth was assessed in the spleen. We demonstrated that social defeat in BCG-infected mice induced a long-term increase in IL-6 and IL-10 production in response to LPS but did not modify the sensitivity of spleen cells to corticosterone. Stress did not affect the specific response to BCG, as shown by the production of cytokines in tuberculin-stimulated cultures. Accordingly, social defeat was unable to influence the mycobacterial growth in vivo. These results support the hypothesis postulating that stress does not affect antigen-specific response when it is applied after priming.

Interleukin-6 as a mechanism for the adverse effects of social stress on acute Theiler’s virus infection

“…Following infection, GCR did not persist in the vehicle treated SDR mice, which is consistent with previous studies (Johnson et al, 2004;Merlot et al, 2004b). Merlot has suggested that infection may reduce the sensitivity of spleen cells to stress, thereby preventing the development of GCR (Merlot et al, 2004b). However, GCR was observed in the TMEV infected SDR mice treated with the IL-6 neutralizing antibody.…”

“…Post hoc analyses indicated that while the vehicle treated SDR and non-stressed groups showed a significant dose-dependent reduction in cell survival, ps < .05, the antibody treated SDR group did not. The finding that GCR did not develop post-infection in the vehicle treated SDR group is consistent with previous work (Johnson et al, 2004;Merlot et al, 2004b). Interestingly, the persistence of GCR in the antibody treated SDR group suggests that neutralizing IL-6 prior to infection increases vulnerability to GCR following infection, despite less severe behavioral and physiological manifestation of acute infection.…”

“…Stressor exposure produces an exaggerated proinflammatory cytokine response to subsequent immune challenge Johnson et al, 2006;Merlot et al, 2004b;Quan et al, 2001), and this response depends on elevations of central proinflammatory cytokine expression during stressor exposure (Johnson et al, 2004). In light of these data, it is tempting to speculate that SDR exacerbates TMEV infection through cross-sensitization or priming of virus-induced cytokine expression during acute infection.…”

“…Other research indicates that stressors can increase circulating and central levels of IL-6 and other proinflammatory cytokines (Johnson et al, 2006;Johnson et al, 2005;Merlot et al, 2004a;Merlot et al, 2004 b;Nguyen et al, 1998;Nguyen et al, 2000;O'Connor et al, 2003;Shintani et al, 1995;Shizuya et al, 1998;Stark et al, 2002;Huang et al, 1997). Moreover, prior exposure to a stressor can potentiate or prolong the release of proinflammatory cytokines following immune challenge Johnson et al, 2006;Merlot et al, 2004b;Quan et a., 2001). These findings suggest that exposure to stress can directly alter immune cell function and promote sustained increases in proinflammatory cytokine production.…”

Birth timing and the mother–infant relationship predict variation in infant behavior and physiology

“…It is also important to note that between the first and second blood samples the infants experienced their mothers' resumption of mating activity, which has been suggested to be a natural form of mother–infant separation (Berman et al, ). The fact that cortisol concentrations prior to the breeding season and at the time of immunization were associated with antibody response, but that cortisol concentrations concurrent with the measurement of antibody were not, emphasizes the fact that conditions at the time of a vaccination, such as greater conflict or stress, can have long lasting effects on immunity (Merlot et al, ). Although the current data differences in immune function, we acknowledge that it is unclear whether these differences would translate into actual differences in disease risk or severity upon exposure to a pathogen.…”