Severe acute malnutrition promotes bacterial binding over proinflammatory cytokine secretion by circulating innate immune cells
Tracy N. Phiri, Kuda Mutasa, Sandra Rukobo, Margaret Govha, Patience Mushayanembwa, Simutanyi Mwakamui, Tafhima Haider, Kanekwa Zyambo, Cherlynn Dumbura, Joice Tome, Thompson Runodamoto, Leah Chidamba, Florence D. Majo, Deophine Ngosa, Kanta Chandwe, Chanda Kapoma, Benjamin Mwapenya, Wadzanai Mufukari, Jonathan P. Sturgeon, Ruairi C. Robertson, Melanie Smuk, Robert Ntozini, Kusum Nathoo, Beatrice Amadi, Paul Kelly, Mutsa Bwakura‐Dangarembizi, Andrew J. Prendergast, Claire D. Bourke
Abstract
Children with severe acute malnutrition (SAM) have high infectious mortality and morbidity, implicating defects in their immune defenses. We hypothesized that circulating innate immune cells from children (0 to 59 months) hospitalized with SAM in Zambia and Zimbabwe ( n = 141) have distinct capacity to respond to bacteria relative to adequately nourished healthy controls ( n = 92). SAM inpatients had higher neutrophil and monocyte Escherichia coli binding capacity but lower monocyte activation and proinflammatory mediator secretion in response to lipopolysaccharide or heat-killed Salmonella typhimurium than controls. Among SAM cases, wasting severity was negatively associated with cytokine secretion, children with HIV had lower monocyte activation, and the youngest children released the least myeloperoxidase upon stimulation. Inpatient bacterial binding capacity and monocyte activation were associated with higher odds of persistent SAM at discharge, a risk factor for subsequent mortality. Thus, SAM shifts innate immune cell function, favoring bacterial containment over proinflammatory activation, which may contribute to health deficits after discharge.