Air Pollution and Undernutrition Induce Rat Alveolar Macrophages Functional Dysregulation and Compromise Their Response to a Viral Challenge.

Air pollution and undernutrition are major global health problems that frequently coexist in vulnerable populations and may interact to impair pulmonary immune defenses. We investigated how chronic undernutrition influences alveolar macrophage (AM) responses to subchronic particulate matter (PM) exposure and their subsequent responsiveness to a viral-like stimulus. Male Wistar rats were assigned to control or nutritional growth retardation (NGR) groups, either ad libitum feeding or a 20% caloric restriction for 4 weeks, respectively. During this period, animals received intranasal Residual Oil Fly Ash (ROFA), a surrogate for airborne PM, or vehicle. Isolated AMs were evaluated for viability, TNFα production, oxidative stress, Nrf2 and LC3 expression, and subsequently challenged with Poly (I:C), a synthetic analog of viral double-stranded RNA. Under basal conditions, AMs from NGR animals exhibited reduced viability and Nrf2 expression, increased TNFα secretion, and elevated LC3 expression compared with controls. In well-nourished animals, ROFA induced similar alterations. However, ROFA produced little or no additional effect in NGR-AMs, indicating an attenuated responsiveness to PM exposure. Following Poly (I:C) stimulation, control AMs mounted an inflammatory response that was further enhanced by prior ROFA exposure, whereas AM from NGR animals displayed an impaired response regardless of ROFA exposure. These findings suggest that chronic undernutrition alters basal AM function and modifies their responsiveness to both PM and subsequent viral-like stimulation. This impaired adaptability may influence innate pulmonary immune defenses and increase susceptibility to respiratory infections in populations simultaneously exposed to undernutrition and air pollution.