Plasmodium chabaudi chabaudi: Effect of Low Parasitemias on Immunity in CB6F1 Mice

Favila-Castillo, L; Monroy-Ostria, Amalia; Garcia-Tapia, David

doi:10.1006/expr.1999.4399

Cited by 6 publications

(7 citation statements)

References 16 publications

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“…Although these results seem to conflict with those reported by Pombo et al (31) showing the absence of specific Abs after a controlled P. falciparum infection, it is worth noting that, in this case, human volunteers were treated with a curative drug schedule immediately after parasite inoculation, leading to ultralow doses of Ag that may have been insufficient to induce the humoral response. In agreement with our results, an improvement of the specific-IgG2a secondary response to P. chabaudi has been previously observed in CB6F1 mice treated with chloroquine when parasitemias reached 1-10% of erythrocytes (32).…”

Section: Discussionsupporting

confidence: 93%

Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

Rosário

Muxel

Rodriguez-Málaga

et al. 2008

The Journal of Immunology

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The mechanisms responsible for the generation and maintenance of immunological memory to Plasmodium are poorly understood and the reasons why protective immunity in humans is so difficult to achieve and rapidly lost remain a matter for debate. A possible explanation for the difficulty in building up an efficient immune response against this parasite is the massive T cell apoptosis resulting from exposure to high-dose parasite Ag. To determine the immunological mechanisms required for long-term protection against P. chabaudi malaria and the consequences of high and low acute phase parasite loads for acquisition of protective immunity, we performed a detailed analysis of T and B cell compartments over a period of 200 days following untreated and drug-treated infections in female C57BL/6 mice. By comparing several immunological parameters with the capacity to control a secondary parasite challenge, we concluded that loss of full protective immunity is not determined by acute phase parasite load nor by serum levels of specific IgG2a and IgG1 Abs, but appears to be a consequence of the progressive decline in memory T cell response to parasites, which occurs similarly in untreated and drug-treated mice with time after infection. Furthermore, by analyzing adoptive transfer experiments, we confirmed the major role of CD4+ T cells for guaranteeing long-term full protection against P. chabaudi malaria.

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Section: Discussionsupporting

confidence: 93%

Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

Rosário

Muxel

Rodriguez-Málaga

et al. 2008

The Journal of Immunology

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“…Subpatent infections with blood-stage Plasmodium chabaudi or Plasmodium yoelii rodent malarias stimulate a good level of immunity, which differed from that induced by patent infection (3,14,15,44). In humans, subpatent infections with a very low inoculum of P. falciparum induce protective immunity (33).…”

Section: Discussionmentioning

confidence: 99%

“…15,2008 ANTIBODY RESPONSES AFTER IPTi WITH SP 1289 designed or powered to test this hypothesis, and further studies are now under way in Manhiça that will help clarify this possibility. Finally, currently we are investigating whether IPTi with SP also has an effect on other types of antibody responses that are thought to be involved in the acquisition of protective immunity to malaria, such as IgG to P. falciparum variant surface antigens and functional growth-inhibitory antibodies.…”

Section: Discussionmentioning

confidence: 99%

Impact of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine on Antibody Responses to Erythrocytic-StagePlasmodium falciparumAntigens in Infants in Mozambique

Quelhas

Puyol

Quintó

et al. 2008

Clin Vaccine Immunol

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We evaluated the impact of intermittent preventive treatment in infants (IPTi) with sulfadoxine-pyrimethamine (SP), which was given at ages 3, 4, and 9 months through the Expanded Program on Immunization (EPI), on the development of antibody responses to Plasmodium falciparum in Mozambique. Immunoglobulin M (IgM) and IgG subclass antibodies specific to whole asexual parasites and to recombinant MSP-1 19 , AMA-1, and EBA-175 were measured at ages 5, 9, 12, and 24 months for 302 children by immunofluorescence antibody tests and by enzyme-linked immunosorbent assays. Antibody responses did not significantly differ between children receiving IPTi with SP and those receiving a placebo at any time point measured, with the exception of the responses of IgG and IgG1 to AMA-1 and/or MSP-1 19 , which were significantly higher in the SP-treated group than in the placebo group at ages 5, 9, and/or 24 months. IPTi with SP given through the EPI reduces the frequency of malarial illness while allowing the development of naturally acquired antibody responses to P. falciparum antigens.Malaria remains one of the major infectious diseases globally, causing up to 3 million deaths and close to 5 billion episodes of clinical illness per year (7). In areas characterized by hyperendemic transmission, the greatest burden of malaria occurs in children less than 12 months of age (38); consequently, infants in sub-Saharan Africa are the main target population for any malaria control tool.Intermittent preventive treatment in infants (IPTi) that consists of the administration of a full dose of an antimalarial within the Expanded Program on Immunization (EPI) has proven to reduce the risk of malaria in this vulnerable group (37). This strategy has gained increasing interest, and several intervention trials evaluating the efficacy of IPTi in the reduction of malaria morbidity have been and are still being carried out in several sub-Saharan countries (Tanzania, Ghana, Senegal, Mozambique, Gabon, and Kenya) as part of an international consortium (www.ipti-malaria.org). However, before setting any policy recommendation for the large-scale implementation of IPTi for malaria control, it is necessary to fully evaluate the consequences that this early preventive intervention may have later in life.An important issue that needs to be considered is the impact that IPTi may have on the development of naturally acquired immunity to malaria. Early studies of continuous malaria chemoprophylaxis raised concerns regarding the loss of or delay in the acquisition of protective immunity (16,23,34). Weekly chemoprophylaxis between 2 and 11 months of age in infants in Tanzania significantly reduced the incidence of malaria and anemia during the first year of life, but the risk increased in the second year after stopping the intervention (26), suggesting that protection against Plasmodium falciparum infection during infancy had delayed the development of immunity to malaria. However, subsequent studies of IPTi in Tanzania (37) and Mozambique (24) showed that, as ...

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“…Mice were fed with Teklad LM‐485 diet (Harlan Sprague Dawley, Indianapolis, IN, USA) and supplied with water ad libitum . As in a previous report (9), we used sex‐ and age‐matched CB6F1 mice of 15–25 weeks old for all experiments because parental strains breed very well in our hands, and F1 hybrids retain the resistance of C57Bl to P. c. chabaudi AS infection.…”

Section: Methodsmentioning

confidence: 99%

“…In contrast, human parasitaemias normally reach levels around 8–10%, and usually results in a short‐term immunity (6–8). These differences may indicate a role of parasitaemia levels on the development of protective immunity, and in fact, one of us has provided evidence that this could be the case in mice (9). CB6F1 mice infected with P. c. chabaudi AS suffer full/high parasitaemias (FP mice) and develop both homologous and heterologous (against the lethal Plasmodium yoelii 17XL) immunity, while mice that are treated with anti‐malarial drug to keep parasitaemias at low levels (LP mice) only develop homologous immunity (9).…”

Section: Introductionmentioning

confidence: 98%

Parasitaemia levels inPlasmodium chabaudiinfected-mice modify IFN-γ and IL-10 expression after a homologous or heterologous challenge

Aguilar‐Medina

Ramos‐Payán

Arámbula-Meraz

et al. 2010

Parasite Immunology

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CB6F1 mice infected with the nonlethal Plasmodium chabaudi chabaudi AS suffer parasitaemia levels up to 40% (full parasitaemia, FP) and develop both homologous and heterologous (against the lethal Plasmodium yoelii 17XL) protective immunity. However, if mice are treated with anti-malarial drug when parasitaemia is below 10% (low parasitaemia, LP), they only develop homologous immunity. For the better understanding of this interesting dissociation related to the degree of parasitaemia, in this work, we studied the genetic expression of some cytokines. We found that during primary parasitaemia both FP and LP mice showed at first a TNF-alpha, IL-2 and IFN-gamma response which is followed by an IL-4 and IL-10 response. When FP and LP mice were challenged with either the homologous (FP + AS and LP + AS mice) or the heterologous parasite (FP + 17XL and LP + 17XL mice), we observed that LP + 17XL mice, which failed to develop heterologous immunity and succumbed to the challenge, showed a stronger IFN-gamma and a weaker IL-10 expression than FP + 17XL mice, which developed heterologous immunity and survived the challenge. The importance and the possible implications of these findings are discussed.

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Plasmodium chabaudi chabaudi: Effect of Low Parasitemias on Immunity in CB6F1 Mice

Cited by 6 publications

References 16 publications

Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

Gradual Decline in Malaria-Specific Memory T Cell Responses Leads to Failure to Maintain Long-Term Protective Immunity to Plasmodium chabaudi AS Despite Persistence of B Cell Memory and Circulating Antibody

Impact of Intermittent Preventive Treatment with Sulfadoxine-Pyrimethamine on Antibody Responses to Erythrocytic-StagePlasmodium falciparumAntigens in Infants in Mozambique

Parasitaemia levels inPlasmodium chabaudiinfected-mice modify IFN-γ and IL-10 expression after a homologous or heterologous challenge

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