Cold Stress-Induced Modulation of Cell Immunity during Acute Toxoplasma gondii Infection in Mice

Abstract

Infection with Toxoplasma gondii in the acute phase results in nonspecific suppression of immunologic function in mice and humans. The present study examined the effects of a physical stressor, i.e., cold stress (CS), on macrophage function (nitrite production, parasite survival) and splenic blastogenesis in the acute phase of murine T. gondii infection. In our stress paradigm, female BALB/c mice were placed in cold water (1 +/- 0.5 C), 5 min each day for 8 days. Nitrite production and parasite survival were measured in cultured peritoneal macrophages obtained from mice subjected to CS after in vivo activation with interferon-gamma/lipopolysaccharide (CS + ACT), and in vitro infection with T. gondii tachyzoites. Peritoneal macrophages from CS + ACT mice showed decreased nitrite production compared to control but activated cells (ACT). Spleen cell proliferation to in vitro stimulation with the mitogens concanavalin A (Con A) and anti-CD3, and Toxoplasma lysate antigen (TLA) was measured in splenocytes obtained from BALB/c mice during the acute phase of infection with T. gondii. Mice subjected to CS and infection (CS + INF) had maximum splenocyte proliferation on days 8 and 15 followed by a subsequent decline on day 28 postinoculation (PI). In contrast, infected mice not subjected to stress (INF) showed decreased splenocyte proliferation on days 8 and 15 followed by an increase on day 28 PI. The rate of mortality was decreased in the CS + INF compared to the INF group during acute infection. These results suggest that CS may alter the pathogenesis of T. gondii infection by modulating acute-phase responses, provoking a state of transient disequilibrium between the host and parasite.

Immunomodulatory Effects of Cold Stress on Mice Infected Intraperitoneally with a 50% Lethal Dose of <i>Toxoplasma gondii</i>

“…This work extends our previous studies on the immunomodulatory effects of CS during T. gondii infection [36,37]. We have shown that macrophages from CS mice produced lower levels of nitric oxide, and had a decreased ability to kill T. gondii compared to infected control mice.…”

“…Cell proliferation was enhanced in CS mice but depressed in the infected group during the 1st week after infection. This effect was reversed during the 2nd week, cell proliferation was enhanced in infected mice, but depressed in CS animals [36]. In addition, CS appeared to have a protective role in mice orally infected with cysts of the ME49 strain of T. gondii [37].…”

“…The stress protocol used in the experiments has been previously described [6,18,36]. Briefly, mice were placed in shallow, clear-glass chambers (5 min each day for 8 days) filled with 2 cm of cold water (1 B 0.5°C), deep enough to cover their backs.…”

“…Tachyzoites were maintained by serial passage in monolayers of human foreskin fibroblasts. Parasites were collected and purified by using a 3-Ìm polycarbonate membrane filter (Millipore, Bedford, Mass., USA) as previously described [36,37]. The PD2 T. gondii strain is a clone of the non-virulent ME49 strain, which has been transfected with the Escherichia coli ß-galactosidase gene [38].…”

T. gondii Infection Acquired during Pregnancy and/or after Birth may be Responsible for Development of both Type 1 and 2 Diabetes Mellitus

“…Several authors showed that cold stress profoundly modulated immune response and the outcome of infections because many mediators released during physical stress, such as glucocorticoids and catecholamines, influenced the growth and multiplication of pathogens, including T. gondii [711,[721][722][723][724]. Cold stress can suppress [725,726] or enhance [727,728] immunity by inducing and/or enhancing the synthesis of specific proteins with relevant roles in transcription, translation, and recombination [729,730].…”