Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and <i>Plasmodium falciparum–</i>Specific Atypical Memory B Cells

Frosch, Anne E.; Odumade, Oludare A.; Jj, Taylor; Ireland, Kathleen F.; Ayodo, George; Ondigo, Bartholomew N.; Narum, David L.; Vulule, John; John, Chandy C.

doi:10.4049/jimmunol.1600773

Cited by 12 publications

(18 citation statements)

References 36 publications

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“…This observation contradicts an earlier study of Gabonese adults, who resided in malaria holoendemic areas, that concluded these B‐cell subsets arose from different precursors . A series of Kenyan studies further support an active role of P. falciparum infections in altering B‐cell subset proportions by expanding transitional B cells and, thereby, interfering with overall B‐cell function. Regardless of lineage, both atypical and classical MBCs have been shown to produce broadly neutralizing antibodies against P. falciparum .…”

Section: Antibody‐mediated Immunity and Cd4 T‐cell Helpcontrasting

confidence: 65%

Immune effector mechanisms in malaria: An update focusing on human immunity

Moormann

Nixon

Forconi

2019

Parasite Immunology

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The past decade has witnessed dramatic decreases in malaria‐associated mortality and morbidity around the world. This progress has largely been due to intensified malaria control measures, implementation of rapid diagnostics and establishing a network to anticipate and mitigate antimalarial drug resistance. However, the ultimate tool for malaria prevention is the development and implementation of an effective vaccine. To date, malaria vaccine efforts have focused on determining which of the thousands of antigens expressed by Plasmodium falciparum are instrumental targets of protective immunity. The antigenic variation and antigenic polymorphisms arising in parasite genes under immune selection present a daunting challenge for target antigen selection and prioritization, and is a given caveat when interpreting immune recall responses or results from monovalent vaccine trials. Other immune evasion strategies executed by the parasite highlight the myriad of ways in which it can become a recurrent infection. This review provides an update on immune effector mechanisms in malaria and focuses on our improved ability to interrogate the complexity of human immune system, accelerated by recent methodological advances. Appreciating how the human immune landscape influences the effectiveness and longevity of antimalarial immunity will help explain which conditions are necessary for immune effector mechanisms to prevail.

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Section: Antibody‐mediated Immunity and Cd4 T‐cell Helpcontrasting

confidence: 65%

Immune effector mechanisms in malaria: An update focusing on human immunity

Moormann

Nixon

Forconi

2019

Parasite Immunology

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“…All HIV-infected individuals who were seen in the voluntary testing and counseling clinic on enrollment dates between May and October 2012 were offered participation in the parent study that examined the immune response to malaria in HIV. 13 Temporally, one HIVuninfected individual was enrolled for every time three HIVinfected individuals were enrolled to ensure that samples from comparison groups were collected with a similar distribution throughout the malaria season. There was a larger number of HIV-infected individuals enrolled so that outcomes could be compared by CD4 count among HIV-infected individuals.…”

Section: Methodsmentioning

confidence: 99%

Iron Deficiency is Prevalent among HIV-Infected Kenyan Adults and is Better Measured by Soluble Transferrin Receptor than Ferritin

Frosch

Ayodo

Odhiambo

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Iron deficiency (ID) and human immunodeficiency virus (HIV) infection frequently coexist. Little data exist on ID in HIV-infected individuals, partly because the iron marker ferritin is altered by inflammation common in HIV infection. We measured iron biomarkers (ferritin, soluble transferrin receptor [sTfR], hepcidin) and red cell indices (hemoglobin, mean corpuscular volume [MCV]) in newly diagnosed, antiretroviral therapy-naive, HIV-infected ( = 138) and uninfected ( = 52) Kenyan adults enrolled in a study of the immune response to malaria. We compared markers between infected and uninfected groups with test and Wilcoxon Rank-Sum, used Spearman correlation to determine the association between iron and inflammatory markers, and applied logistic regression to determine which markers best predicted anemia. HIV-infected individuals had lower hemoglobin ( < 0.001), lower MCV ( < 0.001), higher sTfR ( = 0.003), and a greater prevalence of ID (sTfR > 8.3 mg/L) than uninfected individuals. Ferritin was elevated in HIV-infected individuals and was more strongly correlated with C-reactive protein (ρ = 0.43, < 0.001) and hepcidin (ρ = 0.69, < 0.001) than with hemoglobin. The best predictor of anemia in HIV-infected participants was sTfR, with a one log-unit increase in sTfR associated with a 6-fold increase in the odds of anemia (odds ratio = 6.3, 95% confidence interval: 1.8-21.8). These data suggest a significant burden of ID among treatment-naive HIV-infected Kenyan adults. Soluble transferrin receptor may be a reliable marker of ID in HIV-mediated inflammation.

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“…Of interest, in HIV-malaria coinfected Rwandan adults the expansion of aMBC was greater as compared to that in individuals infected with malaria alone (39). Moreover, Frosch et al (40) showed that in HIV-infected Kenyan adults the proportion of P. falciparum -specific aMBCs in peripheral blood increased as a result of the loss of naïve and resting MBCs. A differential expansion of aMBC was observed in age-matched children living in similar villages in rural Kenya, with the exception of P. falciparum exposure that occurred only in the village in which children showed expansion of aMBCs (35).…”

Section: Introductionmentioning

confidence: 99%

Atypical memory B cells in human chronic infectious diseases: An interim report

Portugal

Obeng-Adjei

Moir

et al. 2017

Cellular Immunology

161

177

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Immunological memory is a remarkable phenomenon in which survival of an initial infection by a pathogen leads to life-long protection from disease upon subsequent exposure to that same pathogen. For many infectious diseases, long-lived protective humoral immunity is induced after only a single infection in a process that depends on the generation of memory B cells (MBCs) and long-lived plasma cells. However, over the past decade it has become increasingly evident that many chronic human infectious diseases to which immunity is not readily established, including HIV-AIDS, malaria and TB, are associated with fundamental alterations in the composition and functionality of MBC compartments. A common feature of these diseases appears to be a large expansion of what have been termed exhausted B cells, tissue-like memory B cells or atypical memory B cells (aMBCs) that, for simplicity’s sake, we refer to here as aMBCs. It has been suggested that chronic immune activation and inflammation drive the expansion of aMBCs and that in some way aMBCs contribute to deficiencies in the acquisition of immunity in chronic infectious diseases. Although aMBCs are heterogeneous both within individuals and between diseases, they have several features in common including low expression of the cell surface markers that define classical MBCs in humans including CD21 and CD27 and high expression of genes not usually expressed by classical MBCs including T-bet, CD11c and a variety of inhibitory receptors, notably members of the FcRL family. Another distinguishing feature is their greatly diminished ability to be stimulated through their B cell receptors to proliferate, secrete cytokines or produce antibodies. In this review, we describe our current understanding of the phenotypic markers of aMBCs, their specificity in relation to the disease-causing pathogen, their functionality, the drivers of their expansion in chronic infections and their life span. We briefly summarize the features of aMBCs in healthy individuals and in autoimmune disease. We also comment on the possible relationship of human aMBCs and T-bet+, CD11c+ age/autoimmune-associated B cells, also a topic of this review volume.

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Decrease in Numbers of Naive and Resting B Cells in HIV-Infected Kenyan Adults Leads to a Proportional Increase in Total and Plasmodium falciparum–Specific Atypical Memory B Cells

Cited by 12 publications

References 36 publications

Immune effector mechanisms in malaria: An update focusing on human immunity

Immune effector mechanisms in malaria: An update focusing on human immunity

Iron Deficiency is Prevalent among HIV-Infected Kenyan Adults and is Better Measured by Soluble Transferrin Receptor than Ferritin

Atypical memory B cells in human chronic infectious diseases: An interim report

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