Malakoplakia is a rare granulomatous disease characterized by the presence of Michaelis-Gutmann bodies on histopathologic analysis. Lesions manifest in a wide range of organs with cutaneous, gastrointestinal and genitourinary systems being most common and often result in significant co-morbidities owing largely to misdiagnoses and the similar appearance to malignancy or granulomatous processes. Most patients are immunocompromised, including the solid organ transplant population. Amongst organ recipients, malakoplakia is most commonly seen in renal transplantation, and only rarely reported in thoracic organ recipients. Here, we report two cases of malakoplakia in thoracic transplant patients that highlight the critical need for tissue diagnosis to avoid delay in management.
Cytomegalovirus (CMV) is an important cause of morbidity and mortality in the immunocompromised host. In transplant recipients, a variety of clinically important “indirect effects” are attributed to immune modulation by CMV, including increased mortality from fungal disease, allograft dysfunction and rejection in solid organ transplantation, and graft-versus-host-disease in stem cell transplantation. Monocytes, key cellular targets of CMV, are permissive to primary, latent and reactivated CMV infection. Here, pairing unbiased bulk and single cell transcriptomics with functional analyses we demonstrate that human monocytes infected with CMV do not effectively phagocytose fungal pathogens, a functional deficit which occurs with decreased expression of fungal recognition receptors. Simultaneously, CMV-infected monocytes upregulate antiviral, pro-inflammatory chemokine, and inflammasome responses associated with allograft rejection and graft-versus-host disease. Our study demonstrates that CMV modulates both immunosuppressive and immunostimulatory monocyte phenotypes, explaining in part, its paradoxical “indirect effects” in transplantation. These data could provide innate immune targets for the stratification and treatment of CMV disease.
One half of cases in Auckland are acquired either from Pacific or locally. Similarities mean that disease acquired locally is likely of Pacific origin.
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