γδ T cells and CD14+ Monocytes Are Predominant Cellular Sources of Cytokines and Chemokines Associated With Severe Malaria

Stanisic, Danielle I.; Cutts, Julia C; Eriksson, Emily M.; Fowkes, Freya J. I.; Rosanas-Urgell, Anna; Siba, Peter; Laman, Moses; Davis, Timothy M. E.; Manning, Laurens; Müeller, Ivo; Schofield, Louis

doi:10.1093/infdis/jiu083

Cited by 65 publications

(104 citation statements)

References 36 publications

Supporting

Mentioning

100

Contrasting

Order By: Relevance

“…al. recently demonstrated a decrease in iRBC-stimulated expression of genes encoding pro-inflammatory cytokines and chemokines in children after their first malaria infection of the season ( 3, 19 ). Because these analyses were performed on bulk unfractionated PBMCs, the cellular subsets responsible for this blunted inflammatory response were not identified.…”

Section: Discussionmentioning

confidence: 99%

Loss and dysfunction of Vδ2 ⁺ γδ T cells are associated with clinical tolerance to malaria

et al. 2014

View full text Add to dashboard Cite

Although clinical immunity to malaria eventually develops among children living in endemic settings, the underlying immunologic mechanisms are not known. The Vδ2+ subset of γδ T cells possess intrinsic reactivity to malaria antigens, can mediate killing of P. falciparum merozoites, and expand markedly in vivo following malaria infection in previously naïve hosts, but their role in mediating immunity in children repeatedly exposed to malaria is unclear. We evaluated γδ T cell responses to malaria among 4-year-old children enrolled in a longitudinal study in Uganda. We found that repeated malaria was associated with reduced percentages of Vδ2+ γδ T cells in peripheral blood, decreased proliferation and cytokine production in response to malaria antigens, and increased expression of immunoregulatory genes. Further, loss and dysfunction of pro-inflammatory Vδ2+ γδ T cells was associated with a reduced likelihood of symptoms upon subsequent P. falciparum infection. Together, these results suggest that repeated malaria infection during childhood results in progressive loss and dysfunction of Vδ2+ γδ T cells that may facilitate immunological tolerance of the parasite.

show abstract

Section: Discussionmentioning

confidence: 99%

Loss and dysfunction of Vδ2 ⁺ γδ T cells are associated with clinical tolerance to malaria

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Brain endothelial cells and astrocytes have been found to express CXCL10 in response to P. berghei ANKA infection (19,20), and high levels of this chemokine have been detected in cerebrospinal fluid of children who succumbed to P. falciparum-mediated CM (14). In addition to brain tissue, recent field studies in malaria-endemic areas revealed strong associations between PBMC-derived CXCL10 and severe malaria, suggesting a role for leukocyte-derived CXCL10 in the development of disease syndromes (34). Consistent with that concept, in this study we found that hematopoietic cell-derived CXCL10 controls leukocyte recruitment to the brain, is responsible for the development of CM, and has a detrimental effect on the control of parasite biomass.…”

Section: Discussionmentioning

confidence: 99%

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

Ioannidis

Nie

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

CXCL10, or IFN-γ–inducible protein 10, is a biomarker associated with increased risk for Plasmodium falciparum–mediated cerebral malaria (CM). Consistent with this, we have previously shown that CXCL10 neutralization or genetic deletion alleviates brain intravascular inflammation and protects Plasmodium berghei ANKA-infected mice from CM. In addition to organ-specific effects, the absence of CXCL10 during infection was also found to reduce parasite biomass. To identify the cellular sources of CXCL10 responsible for these processes, we irradiated and reconstituted wild-type (WT) and CXCL10−/− mice with bone marrow from either WT or CXCL10−/− mice. Similar to CXCL10−/− mice, chimeras unable to express CXCL10 in hematopoietic-derived cells controlled infection more efficiently than WT controls. In contrast, expression of CXCL10 in knockout mice reconstituted with WT bone marrow resulted in high parasite biomass levels, higher brain parasite and leukocyte sequestration rates, and increased susceptibility to CM. Neutrophils and inflammatory monocytes were identified as the main cellular sources of CXCL10 responsible for the induction of these processes. The improved control of parasitemia observed in the absence of CXCL10-mediated trafficking was associated with a preferential accumulation of CXCR3+CD4+ T follicular helper cells in the spleen and enhanced Ab responses to infection. These results are consistent with the notion that some inflammatory responses elicited in response to malaria infection contribute to the development of high parasite densities involved in the induction of severe disease in target organs.

show abstract

“…Similarly to DCs, effector CD8+ T cell response is inhibited during H5N1 viral infection by IL-10 producing CD8+ Treg cells [75,76]. The induced manipulation toward the Th2 profile assures increased surviving possibility for different infective agents, such as viruses, chlamydias, and parasites [65, 67-69, 73,74,[77][78][79]. The early IL-10 production by T cell, B cell, and monocyte/macrophage (but not on NK and DC) activation can lead to chronicity of lymphocytic choriomeningitis and B hepatitis virus infections, and the IL-10-mediated early T cell Similarly to viral infections, parasite-induced IL-10 production by various immune cells is associated with impaired resistance to protozoan and nematodes [80,81,86,87].…”

Section: Principal Immune Conditionsmentioning

confidence: 99%

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

The interleukin-10 (IL-10) is generally considered as the most important cytokine with anti-inflammatory properties and one of the key cytokines preventing inflammation-mediated tissue damage. In this respect, IL-10 producing cells play a crucial role in the outcome of infections, allergy, autoimmune reactions, tumor development, and transplant tolerance. Based on recent findings with regard to the mentioned clinical conditions, this review attempts to shed some light on the IL-10 functions, considering this cytokine as inherent inducer of the switching immunity. While acute infections and vaccinations are associated by IL-10 enhanced during few weeks, chronic parasitoses, tumor diseases, allergen-specific immunotherapy, transplants, and use of immune-suppressor drugs show an increased IL-10 level along months or years. With regard to autoimmune pathologies, the IL-10 increase is prevalently observed during early stages, whereas the successive stages are characterized by reaching of immune equilibrium independently to disease's activity. Together, these findings indicate that IL-10 is mainly produced during transient immune conditions and the persistent IL-10-related effect is the indication/prediction (and maybe effectuation) of the switching immunity. Actual knowledge emphasizes that any manipulation of the IL-10 response for treatment purposes should be considered very cautiously due to its potential hazards to the immune system. Probably, the IL-10 as potential switcher of immunity response should be used in association with co-stimulatory immune effectors that are necessary to determine the appropriate deviation during treatment of respective pathologies. Hopefully, further findings would open new avenues to study the biology of this "master switch" cytokine and its therapeutic potential.

show abstract

γδ T cells and CD14+ Monocytes Are Predominant Cellular Sources of Cytokines and Chemokines Associated With Severe Malaria

Abstract: Early/innate PBMC responses to pRBC in vitro are informative as to cytokines/chemokines associated with SM. Predominant cellular sources are monocytes and γδ T cells. Monocyte-derived chemokines support a role for monocyte infiltrates in the etiology of SM.

Cited by 65 publications

References 36 publications

Loss and dysfunction of Vδ2 ⁺ γδ T cells are associated with clinical tolerance to malaria

Loss and dysfunction of Vδ2 ⁺ γδ T cells are associated with clinical tolerance to malaria

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Contact Info

Product

Resources

About

γδ T cells and CD14+ Monocytes Are Predominant Cellular Sources of Cytokines and Chemokines Associated With Severe Malaria

Abstract: Early/innate PBMC responses to pRBC in vitro are informative as to cytokines/chemokines associated with SM. Predominant cellular sources are monocytes and γδ T cells. Monocyte-derived chemokines support a role for monocyte infiltrates in the etiology of SM.

Cited by 65 publications

References 36 publications

Loss and dysfunction of Vδ2 + γδ T cells are associated with clinical tolerance to malaria

Loss and dysfunction of Vδ2 + γδ T cells are associated with clinical tolerance to malaria

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Contact Info

Product

Resources

About

Loss and dysfunction of Vδ2 ⁺ γδ T cells are associated with clinical tolerance to malaria

Loss and dysfunction of Vδ2 ⁺ γδ T cells are associated with clinical tolerance to malaria