Aspergillus fumigatus is a well adapted, opportunistic fungus that causes a severe and commonly fatal disease, invasive pulmonary aspergillosis (IPA)

Clin Chem Lab Med 2007;45:183–6.

Innate immune molecules such as lung collectins and serum pentraxins have evolved as important host defence proteins against Aspergillus fumigatus, a medically important opportunistic fungal pathogen. Mannan-binding lectin (MBL), an opsonin and lectin complement pathway activator, constitutes another vital player of innate immunity against several pathogenic organisms in the serum. Studies have reported significant binding of MBL to A. fumigatus; however, the protective role of MBL against A. fumigatus-mediated invasive disease remains elusive. Henceforth, we investigated the contribution of externally administered recombinant human (rh) MBL towards anti-fungal defence in invasive pulmonary aspergillosis (IPA) by in vivo and in vitro studies. In murine models of IPA with corticosteroid-induced immunosuppression, rhMBL-treated mice showed 80% survival compared to untreated IPA mice with no survivors. Treated IPA mice also showed a marked increase in tumour necrosis factor (TNF)-α and interleukin (IL)-1α and a significant decrease in pulmonary fungal hyphae and IL-10. In vitro, rhMBL-bound A. fumigatus conidia showed a dose-dependent increase in the deposition of C4b, the first product of the lectin pathway. There was an enhanced uptake of A. fumigatus conidia by the polymorphonuclear cells (PMNs) in the presence of rhMBL that increased further in the presence of MBL supplemented with MBL-deficient serum. However, an increase in the oxidative burst of PMNs and A. fumigatus killing were observed only when MBL was supplemented with MBL-deficient serum. The study suggests a therapeutic role of ex vivo-administered MBL in host defence against aspergillosis, possibly through MBL-mediated complement activation and other protective mechanisms aimed both directly at the pathogen, and indirectly through modulation of the host inflammatory responses.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) has affected millions of people globally. Clinically, it presents with mild flu-like symptoms in most cases but can cause respiratory failure in high risk population. With the aim of unearthing newer treatments, scientists all over the globe are striving hard to comprehend the underlying mechanisms of COVID-19. Several studies till date have indicated a dysregulated host immune response as the major cause of COVID-19 induced mortality. In this Perspective, we propose a key role of endothelium, particularly pulmonary endothelium in the pathogenesis of COVID-19. We draw parallels and divergences between COVID-19-induced respiratory distress and bacterial sepsis-induced lung injury and recommend the road ahead with respect to identification of endothelium-based biomarkers and plausible treatments for COVID-19.