Inefficient tissue immune response against MPXV in an immunocompromised mpox patient.
Jakob MatschkeKristin HartmannSusanne PfefferleYue WangPablo A ValdesEdda ThiesMichaela SchweizerMarc LütgehetmannStefan SchmiedelChristian BernreutherEdward S BoydenMarkus GlatzelSusanne KrasemannPublished in: Journal of medical virology (2024)
The recent outbreak of monkeypox virus (MPXV) was unprecedented in its size and distribution. Those living with uncontrolled HIV and low CD4 T cell counts might develop a fulminant clinical mpox course with increased mortality, secondary infections, and necrotizing lesions. Fatal cases display a high and widespread MPXV tissue burden. The underlying pathomechanisms are not fully understood. We report here the pathological findings of an MPXV-driven abscess in gastrocnemius muscle requiring surgery in an immunocompromised patient with severe mpox. Presence of virus particles and infectivity were confirmed by electron microscopy, expansion microscopy, and virus culture, respectively. MPXV tissue distribution by immunohistochemistry (IHC) showed a necrotic core with infection of different cell types. In contrast, at the lesion rim fibroblasts were mainly infected. Immune cells were almost absent in the necrotic core, but were abundant at the infection rim and predominantly macrophages. Further, we detected high amounts of alternatively activated GPNMB + -macrophages at the lesion border. Of note, macrophages only rarely colocalized with virus-infected cells. Insufficient clearance of infected cells and infection of lesion-associated fibroblasts sustained by the abundance of profibrotic macrophages might lead to the coalescing of lesions and the severe and persistent clinical mpox course observed in immunocompromised patients.
Keyphrases
- induced apoptosis
- immune response
- cell cycle arrest
- electron microscopy
- end stage renal disease
- case report
- minimally invasive
- ejection fraction
- newly diagnosed
- early onset
- hiv infected
- high resolution
- respiratory failure
- skeletal muscle
- single cell
- hiv positive
- risk factors
- chronic kidney disease
- type diabetes
- prognostic factors
- human immunodeficiency virus
- extracellular matrix
- intensive care unit
- cardiovascular events
- peritoneal dialysis
- stem cells
- inflammatory response
- coronary artery bypass
- antibiotic resistance genes
- cell therapy
- coronary artery disease
- magnetic resonance imaging
- microbial community
- single molecule
- percutaneous coronary intervention
- label free
- wastewater treatment
- peripheral blood
- atrial fibrillation
- acute respiratory distress syndrome