Malaria Parasite Infection Compromises Control of Concurrent Systemic Non-typhoidal Salmonella Infection via IL-10-Mediated Alteration of Myeloid Cell Function

Lokken, Kristen L.; Mooney, Jason P.; Butler, Brian P.; Xavier, Mariana N.; Chau, Jennifer; Schaltenberg, Nicola; Begum, Ramie H.; Müller, Werner; Luckhart, Shirley; Tsolis, Renée M.

doi:10.1371/journal.ppat.1004049

Cited by 73 publications

(93 citation statements)

References 67 publications

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“…We next sought to determine a mechanism by which Plasmodium infection prevented virally induced lung inflammatory responses. Recent reports indicate that Plasmodium suppresses immune responses to concurrent infections via IL-10, both during systemic infection with a second lethal Plasmodium species (9, 10) and locally in the gastrointestinal tract during nontyphoidal salmonellosis (7,8). Therefore, we hypothesized that Plasmodium-induced systemic IL-10 inhibits immune responses to respiratory viral coinfection.…”

Section: Pvm Coinfection Does Not Alter the Course Of Blood-stage Pcamentioning

confidence: 98%

“…Indeed, enhanced susceptibility in these Gram-negative bacterial pathogens has also been shown in murine models of malaria (6). These in vivo models also indicate that nonlethal Plasmodium infection elicits a systemic interleukin-10 (IL-10) response, which significantly inhibits subsequent and concurrent immune responses to heterologous pathogens (7)(8)(9)(10). In particular, a recent report shows that macrophage-dependent Plasmodium-induced systemic IL-10 regulates immunity to Salmonella spp.…”

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confidence: 93%

“…In particular, a recent report shows that macrophage-dependent Plasmodium-induced systemic IL-10 regulates immunity to Salmonella spp. in the gas-trointestinal tract (7). Whether such regulatory processes might also inhibit immune responses to concurrent respiratory viral infection remains unclear.…”

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confidence: 99%

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Coinfection with Blood-Stage Plasmodium Promotes Systemic Type I Interferon Production during Pneumovirus Infection but Impairs Inflammation and Viral Control in the Lung

Edwards¹,

Zhang²,

Werder³

et al. 2015

Clin. Vaccine Immunol.

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dAcute lower respiratory tract infections (ALRTI) are the leading cause of global childhood mortality, with human respiratory syncytial virus (hRSV) being a major cause of viral ALRTI in young children worldwide. In sub-Saharan Africa, many young children experience severe illnesses due to hRSV or Plasmodium infection. Although the incidence of malaria in this region has decreased in recent years, there remains a significant opportunity for coinfection. Recent data show that febrile young children infected with Plasmodium are often concurrently infected with respiratory viral pathogens but are less likely to suffer from pneumonia than are non-Plasmodium-infected children. Here, we hypothesized that blood-stage Plasmodium infection modulates pulmonary inflammatory responses to a viral pathogen but does not aid its control in the lung. To test this, we established a novel coinfection model in which mice were simultaneously infected with pneumovirus of mice (PVM) (to model hRSV) and blood-stage Plasmodium chabaudi chabaudi AS (PcAS) parasites. We found that PcAS infection was unaffected by coinfection with PVM. In contrast, PVM-associated weight loss, pulmonary cytokine responses, and immune cell recruitment to the airways were substantially reduced by coinfection with PcAS. Importantly, PcAS coinfection facilitated greater viral dissemination throughout the lung. Although Plasmodium coinfection induced low levels of systemic interleukin-10 (IL-10), this regulatory cytokine played no role in the modulation of lung inflammation or viral dissemination. Instead, we found that Plasmodium coinfection drove an early systemic beta interferon (IFN-␤) response. Therefore, we propose that blood-stage Plasmodium coinfection may exacerbate viral dissemination and impair inflammation in the lung by dysregulating type I IFN-dependent responses to respiratory viruses.A cute lower respiratory tract infections (ALRTI) caused by bacteria and viruses are the leading cause of global childhood mortality. Respiratory syncytial virus (RSV) is a major human pathogen. It is estimated that in 2005, 3.4 million severe cases of RSV-associated ALRTI occurred globally in children Ͻ5 years of age, causing approximately 66,000 to 199,000 deaths; 99% of these occurred in developing countries (1). In sub-Saharan Africa, hundreds of thousands of children Ͻ5 years of age experience severe illnesses each year, not only after infection with RSV, but also due to the Plasmodium species that cause malaria (2, 3). Thus, the combined disease burden for RSV and Plasmodium infections among young children living in sub-Saharan Africa has been very large in the recent past.However, between 2000 and 2012, the incidence of malaria was reduced by 31% and deaths were reduced by 49% in the WHO African Region through the scaling up of various public health initiatives (3). Despite these great achievements, in 2012, 482,000 children under five died as a result of malaria in this region (3). Estimates for the RSV disease burdens over the same time period in sub-Saharan...

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Section: Pvm Coinfection Does Not Alter the Course Of Blood-stage Pcamentioning

confidence: 98%

mentioning

confidence: 93%

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Coinfection with Blood-Stage Plasmodium Promotes Systemic Type I Interferon Production during Pneumovirus Infection but Impairs Inflammation and Viral Control in the Lung

Edwards¹,

Zhang²,

Werder³

et al. 2015

Clin. Vaccine Immunol.

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“…The authors postulated that this outcome was driven largely by uncontrolled oxidative stress brought on by an unchecked immune response. In a second study, the authors recapitulated the likely infection process in areas where the pathogens are endemic by first inducing parisitemia and anemia in mice before orogastrically challenging animals with Salmonella Typhimurium (141). In this staggered secondary infection model, researchers similarly observed high systemic levels of bacteria and parasites, with bacterial replication in the liver significantly increased.…”

Section: Comorbidity Modelsmentioning

confidence: 99%

Animal Models for Salmonellosis: Applications in Vaccine Research

Higginson

Simon

Tennant

2016

Clin Vaccine Immunol

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Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development.A nimal models are indispensable tools for assessing candidate vaccines, with preclinical animal safety, immunogenicity, and efficacy data being prerequisite for regulatory agencies such as the U.S. Food and Drug Administration (FDA) prior to undertaking early-stage clinical trials. However, not all animal models are created equal. While some models are highly robust and closely mimic clinical infection, others are contrived and far removed from clinical relevance. Choosing the right animal model for the vaccine under investigation is imperative in determining its safety and/or effectiveness.Salmonella spp. are often used as model organisms to study bacterial pathogenesis and host-microbe interactions, due to the ability of certain Salmonella serovars to readily infect animals. As such, there are a myriad of animal models available to vaccine developers. These range from colonization or lethality models to those involving complex surgical techniques (Table 1). The choice of model is often related not only to relevance but also cost, ethics, housing requirements, and the availability of appropriate technical expertise. While most researchers utilize one model or another, integration of data from multiple animal models can provide a more complete understanding of the safety of a candidate vaccine and/or predict how a potential vaccine may perform in humans. In this minireview, we provide background on Salmonella clinical syndromes and pathogenesis and then summarize the various animal models that have been used for Salmonella vaccine research. We include a brief discussion of the technical aspects, advantages, and limitations of each model, followed by a review of the literature surrounding its use in vaccine evaluation. While there has been considerable development for veterinary Salmonella vaccines, here we will focus solely on vaccines and models for human salmonellosis.

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“…[28][29][30] IL-10 can, accordingly, suppress the antibacterial immune defense and increase the risk of septicemia. 31 Supporting that IL-10 also plays an important role in cancer-associated immunosuppression, blocking IL-10 activity in combination with immunostimulatory agents can restore antitumor immune responses in animal models with resulting tumor inhibition or regression. [28][29][30] Indeed, IL-10 represses the expression of Th1 cytokines from CTCL cells, and malignant CTCL cells inhibit dendritic cell maturation as well as activation of benign T cells in an IL-10-dependent manner.…”

Section: Introductionmentioning

confidence: 99%