In sub-Saharan Africa, multidrug-resistant non-typhoidal Salmonella serovars are a common cause of fatal bloodstream infection. Malnutrition is a predisposing factor, but the underlying mechanisms are unknown. Here we show that vitamin A deficiency, one of the most prevalent micronutrient deficits afflicting African children, increases susceptibility to disseminated non-typhoidal Salmonella disease in mice and impairs terminal neutrophil maturation.
View Article and Find Full Text PDFBackground: Infertility remains a global reproductive health burden with the highest prevalence in low and middle-income countries. In sub-Saharan Africa, the ability to procreate holds great societal importance. Couples, and particularly women, with infertility can face devastating challenges, leading to social stigma, isolation and/or divorce.
View Article and Find Full Text PDFGastrointestinal symptoms are commonly associated with acute infection. Malaria-associated enteritis may provide an opportunity for enteric pathogens to breach the intestinal mucosa, resulting in life-threatening systemic infections. To investigate whether intestinal pathology also occurs during infection with a murine model of mild and resolving malaria, C57BL/6J mice were inoculated with recently mosquito-transmitted AS.
View Article and Find Full Text PDFBackground: Subclinical infection with Plasmodium falciparum remains highly prevalent, yet diagnosing these often low-density infections remains a challenge. Infections can be subpatent, falling below the limit of detection for conventional thick-film microscopy and rapid diagnostic testing (RDT). In this study, the prevalence of subclinical P.
View Article and Find Full Text PDFRecent malaria is associated with an increased risk of systemic bacterial infection. The aetiology of this association is unclear but malaria-related haemolysis may be one contributory factor. To characterise the physiological consequences of persistent and recently resolved malaria infections and associated haemolysis, 1650 healthy Gambian children aged 8-15 years were screened for infection (by 18sRNA PCR) and/or anaemia (by haematocrit) at the end of the annual malaria transmission season (t).
View Article and Find Full Text PDFMalaria is a systemic febrile disease that may progress to prostration, respiratory distress, encephalopathy, anemia, and death. Malaria is also an established risk factor for invasive bacterial disease caused, in the majority of cases, by invasive enteropathogens and in particular by non-Typhoidal (NTS). Whilst various malaria-related pathologies have been implicated in the risk of NTS bacteraemia in animal models, including intestinal dysbiosis and loss of gut homeostasis, clinical evidence is lacking.
View Article and Find Full Text PDFCD4 αβ T-cells are key mediators of the immune response to a first infection, undergoing extensive activation and splenic expansion during the acute phase of an infection. However, the clonality and clonal composition of this expansion has not previously been described. Using a comparative infection model, we sequenced the splenic CD4 T-cell receptor repertoires generated over the time-course of a infection.
View Article and Find Full Text PDFThe rodent parasite is an important model of malaria. The ability to produce chronic infections makes it particularly useful for investigating the development of anti- immunity, as well as features associated with parasite virulence during both the acute and chronic phases of infection. also undergoes asexual maturation (schizogony) and erythrocyte invasion in culture, so offers an experimentally-amenable to model for studying gene function and drug activity during parasite replication.
View Article and Find Full Text PDFDespite evidence of augmented Natural Killer (NK) cell responses after influenza vaccination, the role of these cells in vaccine-induced immunity remains unclear. Here, we hypothesized that NK cells might increase viral clearance but possibly at the expense of increased severity of pathology. On the contrary, we found that NK cells serve a homeostatic role during influenza virus infection of vaccinated mice, allowing viral clearance with minimal pathology.
View Article and Find Full Text PDFCytokine-induced memory-like (CIML) NK cells generated in response to proinflammatory cytokines in vitro and in vivo can also be generated by vaccination, exhibiting heightened responses to cytokine stimulation months after their initial induction. Our previous study demonstrated that in vitro human NK cell responses to inactivated influenza virus were also indirectly augmented by very low doses of IL-15, which increased induction of myeloid cell-derived cytokine secretion. These findings led us to hypothesize that IL-15 stimulation could reveal a similar effect for active influenza vaccination and influence CIML NK cell effector functions.
View Article and Find Full Text PDFInvasive bacterial disease is well described in immunocompromised hosts, including those with malaria infection. One bacterial infection frequently observed in children with Plasmodium falciparum infection is nontyphoidal salmonella (NTS) infection, in which a typically intestinal infection becomes systemic with serious, often fatal, consequences. In this review, we consider the role of malaria-induced immunoregulatory responses in tipping the balance from tissue homeostasis during malaria infection to risk of invasive NTS.
View Article and Find Full Text PDFUpregulation of haem oxygenase-1 (HO-1), due to haemolysis and/or inflammation, can lead to impaired immune function. Anaemia is common among sepsis patients, but the consequences of sepsis-associated anaemia are poorly understood. Here, our objective was to determine the prevalence and extent of anaemia, haemolysis, inflammation, and HO-1 induction after early hospital admission.
View Article and Find Full Text PDFBackground: The haemolysis associated with clinical episodes of malaria results in the liberation of haem, which activates the enzyme haem oxygenase-1 (HO-1). HO-1 has been shown to reduce neutrophil function and increase susceptibility to invasive bacterial disease. However, the majority of community-associated malaria infections are subclinical, often termed "asymptomatic" and the consequences of low-grade haemolysis during subclinical malaria infection are unknown.
View Article and Find Full Text PDFVaccination has proved to be highly effective in reducing global mortality and eliminating infectious diseases. Building on this success will depend on the development of new and improved vaccines, new methods to determine efficacy and optimum dosing and new or refined adjuvant systems. NK cells are innate lymphoid cells that respond rapidly during primary infection but also have adaptive characteristics enabling them to integrate innate and acquired immune responses.
View Article and Find Full Text PDFType I interferons (IFN-Is) can now be considered as the wedge that balances clinical protection to malaria. New studies recently highlighted a central role for IFN-Is in orchestrating an immunoregulatory network leading to the dampening of proinflammatory responses, expansion of type 1 regulatory (Tr1) cells, and restriction of humoral immunity during malaria blood stage infection. Plasmacytoid dendritic cells (pDCs) were identified as the major source of IFN-Is.
View Article and Find Full Text PDFUnlabelled: Nontyphoidal Salmonella enterica serovar Typhimurium is a frequent cause of bloodstream infections in children and HIV-infected adults in sub-Saharan Africa. Most isolates from African patients with bacteremia belong to a single sequence type, ST313, which is genetically distinct from gastroenteritis-associated ST19 strains, such as 14028s and SL1344. Some studies suggest that the rapid spread of ST313 across sub-Saharan Africa has been facilitated by anthroponotic (person-to-person) transmission, eliminating the need for Salmonella survival outside the host.
View Article and Find Full Text PDFChildhood malaria is a risk factor for disseminated infections with non-typhoidal Salmonella (NTS) in sub-Saharan Africa. While hemolytic anemia and an altered cytokine environment have been implicated in increased susceptibility to NTS, it is not known whether malaria affects resistance to intestinal colonization with NTS. To address this question, we utilized a murine model of co-infection.
View Article and Find Full Text PDFIn immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria.
View Article and Find Full Text PDFNon-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis in immunocompetent individuals, while children with severe Plasmodium falciparum malaria can develop a life-threatening disseminated infection. This co-infection is a major source of child mortality in sub-Saharan Africa. However, the mechanisms by which malaria contributes to increased risk of NTS bacteremia are incompletely understood.
View Article and Find Full Text PDFCoinfection with malaria and nontyphoidal Salmonella serotypes (NTS) can cause life-threatening bacteremia in humans. Coinfection with malaria is a recognized risk factor for invasive NTS, suggesting that malaria impairs intestinal barrier function. Here, we investigated mechanisms and strategies for prevention of coinfection pathology in a mouse model.
View Article and Find Full Text PDFThe development of a topical microbicide blocking the sexual transmission of HIV-1 is urgently needed to control the global HIV/AIDS pandemic. The actinomycete-derived lectin actinohivin (AH) is highly specific to a cluster of high-mannose-type glycans uniquely found on the viral envelope (Env). Here, we evaluated AH's candidacy toward a microbicide in terms of in vitro anti-HIV-1 activity, potential side effects, and recombinant producibility.
View Article and Find Full Text PDFObjective: To identify an HIV epitope suitable for vaccine development.
Design: Diverse HIV-1 strains express few structurally constant regions on their surface vulnerable to neutralizing antibodies. The mostly conserved CD4-binding site (CD4BS) of gp120 is essential for host cell binding and infection by the virus.