Well-Controlled Mucosal Exudation of Undiluted Plasma Proteins Serves Innate and Adaptive Immunity

Distinct from the pulmonary circulation, the human respiratory mucosa is supplied by highly responsive, superficial, systemic microcirculations. In the early symptomatic phase of mucosal infections, circulating peptides-proteins of all sizes are released just beneath the epithelium and will soon appear on the mucosal surface. The traditional view is that mucosal injury must be involved in this plasma exudation process. However, well-controlled human in vivo observations demonstrate that the inflammatory plasma exudation response reflects non-injurious physiologic microvascular-epithelial cooperation. Crucially, although plasma exudation brings unfiltered plasma solutes without size restriction to the mucosal surface this occurs without reducing the protective epithelial barrier against inhaled molecules. Plasma exudation starts early and increases until viral or bacterial infections resolve. Plasma exudation therefore has the potential to slow down, or even prevent, progression to pneumonia and beyond. Plasma exudation would boost efficacy of a mature adaptive immunity by delivering circulating pathogen-neutralising antibodies undiluted to infection spots in the upper airways. Early mucosal infections would thus be dampened and development of lower airway infections prevented. Inferentially, this explains how treatment with vaccines still allows upper airway infections but prevent severe respiratory disease with alveolar and pulmonary circulation injury. Plasma exudation may also contribute to real-life protection against severe influenza/Covid-19 in airway mucosal diseases that exhibit plasma exudation hyperresponsiveness. Such hyperresponsiveness is inducible indicating feasibility of finding future treatments that increase the mucosal innate and adaptive immunity. Altogether, the present synthesis of literature suggests that plasma exudation is an important component of human respiratory mucosal antimicrobial immunity.