Mouse Models for Erythrocytic-Stage Malaria

Sanni, Latifu A.; Fonseca, Luis F.; Langhorne, Jean

doi:10.1385/1-59259-271-6:57

Cited by 43 publications

(47 citation statements)

References 41 publications

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“…These sequelae, combined with elevated parasitemia, are associated with increased mortality from blood-stage malaria infection (42). In the present study, elevated parasitemia at 7 days p.i.…”

Section: Discussionsupporting

confidence: 55%

Involvement of Gonadal Steroids and Gamma Interferon in Sex Differences in Response to Blood-Stage Malaria Infection

et al. 2006

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To examine the hormonal and immunological mechanisms that mediate sex differences in susceptibility to malaria infection, intact and gonadectomized (gdx) C57BL/6 mice were inoculated with Plasmodium chabaudi AS-infected erythrocytes, and the responses to infection were monitored. In addition to reduced mortality, intact females recovered from infection-induced weigh loss and anemia faster than intact males. Expression microarrays and real-time reverse transcription-PCR revealed that gonadally intact females exhibited higher expression of interleukin-10 (IL-10), IL-15R␣, IL-12R␤, Gadd45␥, gamma interferon (IFN-␥), CCL3, CXCL10, CCR5, and several IFN-inducible genes in white blood cells and produced more IFN-␥ than did intact males and gdx females, with these differences being most pronounced during peak parasitemia. Intact females also had higher anti-P. chabaudi immunoglobulin G (IgG) and IgG1 responses than either intact males or gdx females. To further examine the effector mechanisms mediating sex differences in response to P. chabaudi infection, responses to infection were compared among male and female wild-type (WT), T-cell-deficient (TCR␤␦ ؊/؊ ), B-cell-deficient (MT), combined T-and B-cell-deficient (RAG1), and IFN-␥ knockout (IFN-␥ ؊/؊ ) mice. Males were 3.5 times more likely to die from malaria infection than females, with these differences being most pronounced among TCR␤␦ ؊/؊ , MT, and RAG1 mice. Male mice also exhibited more severe weight loss, anemia, and hypothermia, and higher peak parasitemia than females during infection, with WT, RAG1, TCR␤␦ ؊/؊ , and MT mice exhibiting the most pronounced sexual dimorphism. The absence of IFN-␥ reduced the sex difference in mortality and was more detrimental to females than males. These data suggest that differential transcription and translation of IFN-␥, that is influenced by estrogens, may mediate sex differences in response to malaria.Males are more susceptible to many protozoan infections than females and field and laboratory studies link increased susceptibility to infection with circulating steroid hormones (17,18,39). One genus of protozoan parasites that causes a pronounced sexual dimorphism in vertebrate hosts is Plasmodium. Among humans, although the incidence of infection is often similar between the sexes (see references 51 and 52), sex differences in the intensity of infection are reported in which men have higher parasitemia than women (23, 32, 52). The observation that P. falciparum (i.e., a human malaria parasite) density increases at puberty in men, but not in women, suggests that circulating sex steroids may influence this outcome (23).Studies of rodent malarias have confirmed that males are more likely to die after blood-stage malaria infection than are females (2,3,(54)(55)(56)

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Section: Discussionsupporting

confidence: 55%

Involvement of Gonadal Steroids and Gamma Interferon in Sex Differences in Response to Blood-Stage Malaria Infection

et al. 2006

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“…Two weeks after being infected by aerosol with M. tuberculosis CDC1551, mice were infected by intraperitoneal injection with 10 5 P. yoelii 17XL-parasitized erythrocytes suspended in PBS. Parasitemia was monitored by daily examination of Giemsa-stained thin smears of whole blood (47). P. yoelii antigen preparation.…”

Section: Methodsmentioning

confidence: 99%

Mycobacterium-Induced Potentiation of Type 1 Immune Responses and Protection against Malaria Are Host Specific

et al. 2005

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Malaria and tuberculosis are endemic in many regions of the world, and coinfection with the two pathogens is common. In this study, we examined the effects of long-and short-term infection with Mycobacterium tuberculosis on the course of a lethal form of murine malaria in resistant (C57BL/6) and susceptible (BALB/c) mice. C57BL/6 mice coinfected with M. tuberculosis CDC1551 and Plasmodium yoelii 17XL had a lower peak parasitemia and increased survival compared to mice infected with P. yoelii 17XL alone. Splenic microarray analysis demonstrated potentiation of type 1 immune responses in coinfected C57BL/6 mice, which was especially prominent 5 days after infection with P. yoelii 17XL. Splenocytes from coinfected C57BL/6 mice produced higher levels of gamma interferon (IFN-␥) and tumor necrosis factor alpha than splenocytes from mice infected with either pathogen alone. Interestingly, mycobacterium-induced protection against lethal P. yoelii is mouse strain specific. BALB/c mice were significantly more susceptible than C57BL/6 mice to infection with P. yoelii 17XL and were not protected against lethal malaria by coinfection with M. tuberculosis. In addition, M. tuberculosis did not augment IFN-␥ responses in BALB/c mice subsequently infected with P. yoelii 17XL. These data indicate that M. tuberculosis-induced potentiation of type 1 immune responses is associated with protection against lethal murine malaria.

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“…Scientists should use the most appropriate model for their particular research question and take advantage of their particular knowledge about compounds to be tested, especially in terms of molecular and/or biological targets. A rather rich presentation of experimental malaria infections in different mouse strains, comprising some models for cerebral malaria, can be found in (Sanni et al, 2002).…”

Section: Designing An Experimental Mouse Modelmentioning

confidence: 99%