Plasmodium chabaudi chabaudi:Differential Susceptibility of Gene-Targeted Mice Deficient in IL-10 to an Erythrocytic-Stage Infection

Linke, A; Kühn, Ralf; Müller, Werner; Honarvar, Naveed; Li, Ching; Langhorne, Jean

doi:10.1006/expr.1996.0111

Cited by 93 publications

(90 citation statements)

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“…Intriguingly, as observed here and previously, the gender difference in response to P. chabaudi AS infection is more prominent in cytokine-or cytokine receptor-deficient mice (18,29). Further studies are required to understand the interactions between sex hormones and the immune response during blood-stage malaria.…”

Section: Discussionsupporting

confidence: 88%

“…Fluorescence-activated cell sorter analysis of nucleated spleen cells showed that the recruitment and/or local proliferation of NK cells and F4/80 ϩ macrophages expressing Ia antigen were deficient in infected male and female GKO mice compared to their WT counterparts. Studies of P. chabaudi AS-infected IL-10 deficient mice showed that increased mortality among these mice is accompanied by an enhanced Th1 IFN-␥ response during acute infection which is retained in the chronic phase of infection (18). Th1 cytokine responses are also sustained during P. chabaudi AS infection in IL-4-deficient mice compared to WT littermates (44).…”

Section: Discussionmentioning

confidence: 99%

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Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-StagePlasmodium chabaudiAS Infection

2000

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The role of endogenous gamma interferon (IFN-␥) in protective immunity against blood-stage Plasmodium chabaudi AS malaria was studied using IFN-␥ gene knockout (GKO) and wild-type (WT) C57BL/6 mice. Following infection with 10 6 parasitized erythrocytes, GKO mice developed significantly higher parasitemia during acute infection than WT mice and had severe mortality. In infected GKO mice, production of interleukin 12 (IL-12) p70 and tumor necrosis factor alpha in vivo and IL-12 p70 in vitro by splenic macrophages was significantly reduced compared to that in WT mice and the enhanced nitric oxide (NO) production observed in infected WT mice was completely absent. WT and GKO mice had comparable numbers of total nucleated spleen cells and B220؉ and Mac-1 ؉ spleen cells both before and after infection. Infected WT mice, however, had significantly more F4/80 ؉ , NK1.1 ؉ , and F4/80 ؉ Ia ؉ spleen cells than infected GKO mice; male WT had more CD3؉ cells than male GKO mice. In comparison with those from WT mice, splenocytes from infected GKO mice had significantly higher proliferation in vitro in response to parasite antigen or concanavalin A stimulation and produced significantly higher levels of IL-10 in response to parasite antigen. Infected WT mice produced more parasite-specific immunoglobulin M (IgM), IgG2a, and IgG3 and less IgG1 than GKO mice. Significant gender differences in both GKO and WT mice in peak parasitemia levels, mortality, phenotypes of spleen cells, and proliferation of and cytokine production by splenocytes in vitro were apparent during infection. These results thus provide unequivocal evidence for the central role of endogenous IFN-␥ in the development of protective immunity against blood-stage P. chabaudi AS.Studies of experimental murine models as well as humans suggest an important role for gamma interferon (IFN-␥) in protective immune responses to blood-stage malaria (19,22). Treatment of mice with exogenous IFN-␥ delays the onset of parasitemia and decreases the number of infected erythrocytes during Plasmodium chabaudi adami infection (4). Shear and her colleagues (31) demonstrated that daily treatment with recombinant IFN-␥ resulted in a less severe course of infection and increased survival in mice infected with the lethal strain of Plasmodium yoelii 17x. Furthermore, these investigators found a correlation between the timing and level of IFN-␥ production in vitro by spleen cells and the outcome of infection with lethal versus nonlethal strains of P. yoelii 17x. These observations were confirmed in a recent study demonstrating that endogenous levels of IFN-␥ in the spleen during blood-stage malaria infection differ between nonlethal and lethal Plasmodium species at 24 h after infection (5). Studies in our laboratory of resistant C57BL/6 and susceptible A/J mice demonstrated a correlation between the level of resistance to blood-stage P. chabaudi AS infection and IFN-␥ mRNA expression and protein production by spleen cells (15,27,34). In addition, treatment of P. chabaudi AS-infected C57BL...

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-StagePlasmodium chabaudiAS Infection

2000

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“…[33][34][35][36] Mouse studies have consistently shown IL-10 to be an important cytokine in decreasing inflammation and protecting the host in murine malaria models. [37][38][39] In human malaria, several studies have demonstrated association of low IL-10 levels with more severe disease such as cerebral malaria and severe anemia. 37,40,41 Elevated levels of IL-10 have been associated with clinical protection from these severe manifestations of malaria 37 at the expense of persistent and/or elevated parasitemia.…”

Section: Discussionmentioning

confidence: 99%

Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

Abeles¹,

Chuquiyauri²,

Tong³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Infection of mosquitoes by humans is not always successful in the setting of patent gametocytemia. This study tested the hypothesis that pro-or anti-inflammatory cytokines are associated with transmission of Plasmodium vivax to Anopheles darlingi mosquitoes in experimental infection. Blood from adults with acute, non-severe P. vivax malaria was fed to laboratory-reared F1 An. darlingi mosquitoes. A panel of cytokines at the time of mosquito infection was assessed in patient sera and levels compared among subjects who did and did not infect mosquitoes. Overall, blood from 43 of 99 (43%) subjects led to mosquito infection as shown by oocyst counts. Levels of IL-10, IL-6, TNF-α, and IFN-γ were significantly elevated in vivax infection and normalized 3 weeks later. The anti-inflammatory cytokine IL-10 was significantly higher in nontransmitters compared with top transmitters but was not in TNF-α and IFN-γ. The IL-10 elevation during acute malaria was associated with P. vivax transmission blocking.

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“…78,79 Furthermore, a number of polymorphisms in the human TNF-␣ promoter show greater association with anemia than with cerebral malaria. 80 The IL-10/ TNF-␣ ratio is also important in mice where IL-10 knock-out mice infected with P chabaudi display increased anemia, 81 which is reversed following TNF-␣ neutralization in vivo. 82 It is therefore conceivable that in both humans and mice, IL-10 may protect against bone marrow suppression and erythrophagocytic activity induced by TNF-␣ and/or mitigate other proinflammatory stimuli.…”

Section: Erythropoietic Suppression and Dyserythropoiesismentioning

confidence: 99%

“…In mice, massive splenomegaly is observed with cellularity increasing 20-fold at peak parasitemia compared with that of naive animals. 64,81 This rise is reflected in greater erythroid progenitor populations with up to an 8-fold increase of BFU-E and 100-fold increase of CFU-E total numbers in the spleen. 65,66 Interestingly, there is a strong correlation between the severity of disease and the observed increases in splenic erythropoiesis.…”

Section: Org Frommentioning

confidence: 99%

Malarial anemia: of mice and men

Lamikanra

Brown²,

Potocnik³

et al. 2007

Blood

Self Cite

228

215

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Severe malaria is manifest by a variety of clinical syndromes dependent on properties of both the host and the parasite. In young infants, severe malarial anemia (SMA) is the most common syndrome of severe disease and contributes substantially to the considerable mortality and morbidity from malaria. There is now growing evidence, from both human and mouse studies of malaria, to show that anemia is due not only to increased hemolysis of infected and clearance of uninfected red blood cells (RBCs) but also to an inability of the infected host to produce an adequate erythroid response. In this review, we will summarize the recent clinical and experimental studies of malaria to highlight similarities and differences in human and mouse pathology that result in anemia and so inform the use of mouse models in the study of severe malarial anemia in humans. Malaria in humansThe vast majority of morbidity and mortality from malaria is caused by infection with Plasmodium falciparum, although P vivax, P ovale, and P malariae also are responsible for human infections. The total burden of disease has recently been estimated to 515 million episodes annually and malaria is responsible for 18% of all childhood deaths in sub-Saharan Africa, equivalent to 800 000 deaths each year. 1,2 The study of malarial anemia has somewhat belatedly excited academic and professional interest. Severe malarial anemia (SMA) certainly merits concern as a major public health problem because of the very large numbers of children affected, and it is likely that these numbers may increase as drug resistance spreads. Concerns have also been raised by data from recent vaccine studies, which suggest that monkeys immunized with erythrocytic-stage antigens, and that have acquired protection from acute infection, may succumb to severe anemia during a subacute or chronic phase of infection. 3,4 Moreover, there is increasing awareness of the difficulty of satisfactory treatment by blood transfusion outside specialist centers in many endemic areas as a result of the limited availability of a rapid and safe supply of blood. 1,5 SMA is seen most frequently in areas of very high malaria transmission and most commonly in young children and pregnant women. 6 The prevalence of anemia, defined as a hematocrit (Hct) level higher than 0.33, in malaria-endemic areas of Africa, varies between 31% and 91% in children, and between 60% and 80% in pregnant women. 7,8 Given the high degree of morbidity that is associated with SMA in children, this term will be used to refer to severe anemia in this group, unless stated otherwise.It is very difficult to determine the number of cases of severe anemia attributable to malaria as the WHO definition of SMA (a hemoglobin [Hb] concentration of Ͻ 50 g/L [5 g/dL], or a Hct Ͻ 0.15, in the presence of a parasitemia Ͼ 10 000 parasites per microliter [L], and a normocytic blood film) may exclude the considerable proportion of children admitted with severe anemia that has a blood smear negative for malaria parasites but that responds to an...

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Plasmodium chabaudi chabaudi:Differential Susceptibility of Gene-Targeted Mice Deficient in IL-10 to an Erythrocytic-Stage Infection

Cited by 93 publications

References 0 publications

Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-StagePlasmodium chabaudiAS Infection

Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-StagePlasmodium chabaudiAS Infection

Human Host-Derived Cytokines Associated with Plasmodium vivax Transmission from Acute Malaria Patients to Anopheles darlingi Mosquitoes in the Peruvian Amazon

Malarial anemia: of mice and men

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