United States: The COVID-19 has always being a concern for health experts and authorities, however the worries were decreased – which have once again increased as a recent research has revealed that the infection could result in pneumonia.
Accordingly, the lungs’ guardians are responsible for protection against any infection attacking the body organ, and their reactions can help in explaining why the COVID-19 infection is severe, according to Health Daily, ScienceNews.
Amidst the pulmonary expanse, custodial sentinels, designated as interstitial macrophages, traverse vigilantly. Revelations by researchers disclosed online on April 10 in the Journal of Experimental Medicine unveiled the susceptibility of these entities to substantial infection by SARS-CoV-2. In the throes of the viral onslaught, the hyperactive inflammatory retort of these cells potentially contributes to the inception of pneumonia, a malady inflicting detriment upon pulmonary integrity and impeding respiratory efficacy.
“The intricacies surrounding the initial retorts of human pulmonary tissue to a SARS-CoV-2 incursion remain enigmatic,” remarks José Ordovás–Montañés, an adept in immunology at Boston Children’s Hospital and Harvard Medical School, unaffiliated with the study. This recent endeavor has “focused attention” on the involvement of interstitial macrophages, he posits.
The expert further stated, “It introduces a compelling element to the puzzle.”
The onset of COVID-19 transpired subsequent to inhalation of the coronavirus, disseminated via sneezing or coughing, thereby traversing atmospheric domains (SN: 12/16/21). Indications suggest the virus preferentially infects epithelial cells lining the nasopharynx or oropharynx, inciting an immunological counteroffensive.
While many individuals surmount the infection at this juncture, delineates Catherine Blish, a viral immunologist at Stanford University School of Medicine, a faction succumbs to continued infection, whereupon the virus infiltrates the pulmonary bronchioles and infects alveolar epithelial cells, the sites of gaseous exchange, as reported by ScienceNews.
Blish and associates embarked on a quest to scrutinize subsequent phases of coronavirus propagation within the pulmonary microenvironment and the precipitating factors culminating in pneumonia. Employing diminutive sections of human pulmonary tissue procured from postmortem organ donations or surgical resections, the investigators subjected the specimens to SARS-CoV-2, discerning cellular targets of infection. “The outcome was unequivocal,” asserts Blish. Predominantly targeted were macrophages and phagocytic leukocytes tasked with antigen presentation to elicit immune responses.
Conspicuously, two subsets of macrophages were identified: interstitial macrophages entrenched within pulmonary parenchyma and those associated with alveolar cavities. Subsequent experiments involved isolating macrophages of each variety and exposing them to SARS-CoV-2, corroborating infection susceptibility. Concomitantly, the immune reaction of both macrophage subtypes was evaluated. Whereas alveolar macrophages displayed a commensurate inflammatory response, interstitial counterparts succumbed to viral domination, augmenting antiviral protein synthesis and recruiting immune reinforcements. This elicited a cascading alarm, signaling an imminent threat.
Such immune hyperactivity within the pulmonary milieu precipitates a deluge of leukocytes and inflammatory mediators into alveolar spaces, compromising gas exchange and fostering pneumonic predisposition, elucidates Blish. Additionally, the study elucidates an alternative entry mechanism for SARS-CoV-2 into interstitial macrophages, distinct from the canonical ACE2 receptor, potentially explaining the inefficacy of ACE2-targeting therapeutics in severe pneumonia management.
However, the limitations of ex vivo lung slice experimentation preclude precise replication of in vivo intricacies, contends Blish. Crucially, the study overlooks the route of viral ingress into the pulmonary interstitium and subsequent macrophage engagement, warranting further investigation.
“It presents a cogent hypothesis,” acknowledged Ordovás–Montañés. Nonetheless, the egalitarian nature of lung slice experimentation confers equal susceptibility to all resident cell populations, necessitating complementary investigations in intact animal models to delineate the true physiological nuances, albeit acknowledging the inherent limitations in extrapolating findings to human pathophysiology. “Each model imparts a slightly skewed vantage of reality.”