Variation in Morbidity and Mortality of Murine Typhus Infection in Mice With Changes in the Environmental Temperature

Abstract

Experiments reported in the preceding paper have shown that murine typhus rickettsiae cause a uniformly fatal rickettsial peritonitis in the dba strain of mice, while in other strains, under identical environmental conditions, the mortality is less than 60 per cent. In the course of this work, it became apparent that relatively slight changes in room temperature had a marked influence on the course of the infection. Data showing this effect will be summarized in this paper. EXPERIMENTALIn all, 105 mice of mixed sexes were injected intraperitoneally with light, heavy, or massive doses of murine typhus rickettsiae, and maintained at different temperatures. Some animals were kept in an artificially cooled room in which the temperature varied between 65 ° and 73°F. The remainder of the animals were kept in a room in which the temperature was dependent on climatic variation. Some experiments were done during relatively cool spring weather, during which the temperature range was between 70 ° and 80°F. Other experiments were done during heat waves, with temperatures in the animal room ranging from 85-98°F.Of the 105 mice included in this analysis, only 44 represent parallel experiments. Twenty-two of these were kept at 65-73°F. and the other 22, injected with identical inocula, (brain tissue from dba mice dead or dying after intraperitoneal inoculation), were kept at 85-98°F. (approximate). The mortality in the cooler room was 100 per cent while only 2 of 22 animals in the warm room died. The other 61 mice represent experiments which were not strictly parallel, since several different batches of inoculum were used.Smears were made from the peritoneal cavity of each mouse dying, and animals in which huge numbers of rickettsiae were found, without evidence of secondary infection, were regarded as having died of typhus. RESULTSThe results are summarized in Table I. With massive or heavy doses, intraperitoneally injected dba mice invariably died when kept at 70--80°F. (approximate). Even with light dosage, death occurred in all dba mice injected intraperitoneally and kept at 65-73°F. In a very warm room (85-98°F. approximate) 9 out of 13 mice survived following heavy dosage and 20 out of 22 following light dosage. A definite lengthening of the incubation period and prolongation of life was noted in animals dying in the warm room.

Thermoneutral Housing Accelerates Metabolic Inflammation to Potentiate Atherosclerosis but Not Insulin Resistance

“…Previous studies have shown that ambient temperature has a profound effect on the physiological responses of mice to infection, tumors, and aging. This was first noted during studies with experimental murine typhus in the 1940’s when changes in laboratory’s ambient temperature were found to strongly affect the mortality of mice: a shift from 9% at T a of 29.4–36.7°C to 100% at T a of 18.3–22.8°C (Moragues and Pinkerton, 1944). In subsequent studies, it was found that mice housed at warmer temperatures had better immunity against bacterial, viral, and protozoal infections (Amrein, 1967; Bell and Moore, 1974; Miraglia and Berry, 1962; Previte and Berry, 1962; Underwood et al, 1966).…”

Warming the mouse to model human diseases

“…As the temperature in the laboratory became cooler (29.4–36.6°C in summer to 18.3–22.8°C in winter), mortality rose from 9 to 100%. Although these were anecdotal observations, others have reported a similar decline in host immunity against bacterial ( Salmonella typhimurium, Staphylococcus aureus, Klebsiella pneumonia , and Rickettsia typhi ), viral (influenza virus, herpes simplex virus, and rabies virus), and protozoal ( Trypanosoma cruzi ) infections at cooler housing temperatures 73-80 . The effects of the cold housing environment are not limited to host responses to pathogenic infections, because dramatic reorganization of the gut microbial communities has been reported in cold-acclimated mice.…”

“…Studies dating back to 1940’s indicate that the housing T a of mice has a profound effect on host immune responses to infections. For example, Moragues and Pinkerton noted that weather-dependent changes in ambient housing temperature affected the survival of mice during experimental typhus 73 . As the temperature in the laboratory became cooler (29.4–36.6°C in summer to 18.3–22.8°C in winter), mortality rose from 9 to 100%.…”

Temperature Matters! And Why It Should Matter to Tumor Immunologists

“…Recent research shows that there is a large bio-energetic cost associated with generating effective T cell-mediated immune response (49–51). A weakened immune response and an increased incidence of infectious diseases during cold exposure have often been observed in animals in the wild and in experimental situations (52–54). Based on these findings, it has been suggested that when immunological defenses are too energetically costly (55–57), they are selectively “traded off” in favor of higher priority functions such as thermoregulation.…”