Antibodies targeting merozoites induce natural killer cell degranulation and interferon gamma secretion and are associated with immunity against malaria

Natural killer cells are potent immune effectors that can be activated via antibody mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that natural killer (NK) cells degranulate and release IFNγ upon stimulation with antibody-opsonized Plasmodium falciparum merozoites. Antibody-dependent NK activity (Ab-NK) was largely strain-transcending and enhanced the inhibition of invasion into erythrocytes. Ab-NK was associated with the successful control of parasitemia following experimental malaria challenge in African adults. In an independent cohort study in children, Ab-NK increased with age, was boosted by concurrent falciparum infections and associated with a lower risk of clinical episodes of malaria. Nine of 14 vaccine candidates tested induced Ab-NK including some less well-studied antigens - P41, P113, MSP11, RHOPH3, and Pf_11363200. These data highlight an important role for ab-NK in immunity against malaria and provide a new mechanism for the evaluation of vaccine candidates.

Dietary Supplementation with Biobran/MGN-3 Increases Innate Resistance and Reduces the Incidence of Influenza-like Illnesses in Elderly Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Clinical Trial

Influenza-like illness (ILI) remains a major cause of severe mortality and morbidity in the elderly. Aging is associated with a decreased ability to sense pathogens and mount effective innate and adaptive immune responses, thus mandating the development of protective nutraceuticals. Biobran/MGN-3, an arabinoxylan from rice bran, has potent anti-aging and immunomodulatory effects, suggesting that it may be effective against ILI. The objective of the current study was to investigate the effect of Biobran/MGN-3 on ILI incidence, natural killer (NK) cell activity, and the expressions of RIG-1 (retinoic acid-inducible gene 1), MDA5 (melanoma differentiation-associated protein 5), and their downstream signaling genes ISG-15 (interferon-stimulated genes 15) and MX1 (myxovirus (influenza) resistance 1, interferon-inducible). A double-blind, placebo-controlled clinical trial included eighty healthy older adults over 55 years old, 40 males and 40 females, who received either a placebo or Biobran/MGN-3 (500 mg/day) for 3 months during known ILI seasonality (peak incidence) in Egypt. The incidence of ILI was confirmed clinically according to the WHO case definition criteria. Hematological, hepatic, and renal parameters were assessed in all subjects, while the activity of NK and NKT (natural killer T) cells was assessed in six randomly chosen subjects in each group by the degranulation assay. The effect of Biobran/MGN-3 on RIG-1 and MDA5, as well as downstream ISG15 and MX1, was assessed in BEAS-2B pulmonary epithelial cells using flow cytometry. The incidence rate and incidence density of ILI in the Biobran/MGN-3 group were 5.0% and 0.57 cases per 1000 person-days, respectively, compared to 22.5% and 2.95 cases per 1000 person-days in the placebo group. Furthermore, Biobran/MGN-3 ingestion significantly enhanced NK activity compared to the basal levels and to the placebo group. In addition, Biobran/MGN-3 significantly upregulated the expression levels of RIG-1, MDA5, ISG15, and MX1 in the human pulmonary epithelial BEAS-2B cell lines. No side effects were observed. Taken together, Biobran/MGN-3 supplementation enhanced the innate immune response of elderly subjects by upregulating the NK activity associated with reduction of ILI incidence. It also upregulated the intracellular RIG-1, MDA5, ISG15, and MX1 expression in pulmonary epithelial tissue cultures. Biobran/MGN-3 could be a novel agent with prophylactic effects against a wide spectrum of respiratory viral infections that warrants further investigation.

NK Cell Subpopulations and Receptor Expression in Recovering SARS-CoV-2 Infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or pauci symptomatic, extremely severe clinical forms are observed. In this case complex immune dysregulations and an excessive inflammatory response are observed and are the main cause of morbidity and mortality. Natural Killer cells are key players in the control of viral infection and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 in-patients suffering from chronic neurological conditions who recovered from mild, moderate or severe SARS-CoV-2 infection comparing the results to those of 10 SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection; an increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.

NK Cell Subpopulations and Receptor Expression in Recovering SARS-CoV-2 Infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or pauci symptomatic, extremely severe clinical forms are observed. In this case complex immune dysregulations and an excessive inflammatory response are observed and are the main cause of morbidity and mortality. Natural Killer cells are key players in the control of viral infection and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 in-patients suffering from chronic neurological conditions who recovered from mild, moderate or severe SARS-CoV-2 infection comparing the results to those of 10 SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection; an increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.

NK Cell Subpopulations and Receptor Expression in Recovering SARS-CoV-2 Infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic of coronavirus disease (COVID-19). Whereas in most cases COVID-19 is asymptomatic or pauci symptomatic, extremely severe clinical forms are observed. In this case complex immune dysregulations and an excessive inflammatory response are observed and are the main cause of morbidity and mortality. Natural Killer cells are key players in the control of viral infection and their activity is regulated by a tight balance between activating and inhibitory receptors; an alteration of NK activity was suggested to be associated with the development of severe forms of COVID-19. In this study we analyzed peripheral NK cell subpopulations and the expression of activating and inhibitory receptors in 30 in-patients suffering from chronic neurological conditions who recovered from mild, moderate or severe SARS-CoV-2 infection comparing the results to those of 10 patients SARS-CoV-2-uninfected patients. Results showed that an expansion of NK subset with lower cytolytic activity and an augmented expression of the 2DL1 inhibitory receptor, particularly when in association with the C2 ligand (KIR2DL1-C2), characterized the immunological scenario of severe COVID-19 infection; an increase of NK expressing the ILT2 inhibitory receptor was instead seen in patients recovering from mild or moderate infection compared to controls. Results herein suggest that the KIR2DL1-C2 NK inhibitory complex is a risk factor toward the development of severe form of COVID-19. Our results confirm that a complex alteration of NK activity is present in COVID-19 infection and offer a molecular explanation for this observation.