RESUMEN
We report a case of inflammatory colitis after SARS-CoV-2 infection in a patient with no additional co-morbidity who died within three weeks of hospitalization. As it is becoming increasingly clear that SARS-CoV-2 infection can cause immunological alterations, we investigated the expression of the inhibitory checkpoint PD-1 and its ligand PD-L1 to explore the potential role of this axis in the break of self-tolerance. The presence of the SARS-CoV-2 virus in colon tissue was demonstrated by qRT-PCR and immunohistochemical localization of the nucleocapsid protein. Expression of lymphocyte markers, PD-1, and PD-L1 in colon tissue was investigated by IHC. SARS-CoV-2-immunoreactive cells were detected both in the ulcerated and non-ulcerated mucosal areas. Compared to healthy tissue, where PD-1 is weakly expressed and PD-L1 is absent, PD-1 and PD-L1 expression appears in the inflamed mucosal tissue, as expected, but was mainly confined to non-ulcerative areas. At the same time, these markers were virtually undetectable in areas of mucosal ulceration. Our data show an alteration of the PD-1/PD-L1 axis and suggest a link between SARS-CoV-2 infection and an aberrant autoinflammatory response due to concomitant breakdown of the PD-1/PD-L1 interaction leading to early death of the patient.
Asunto(s)
COVID-19/inmunología , Colitis/inmunología , Colon/metabolismo , Síndrome de Liberación de Citoquinas/inmunología , Inflamación/inmunología , SARS-CoV-2/fisiología , Anciano , Antígeno B7-H1/metabolismo , Colon/patología , Resultado Fatal , Femenino , Humanos , Receptor de Muerte Celular Programada 1/metabolismo , Autotolerancia , Transducción de SeñalRESUMEN
In this study, a new syngeneic murine neuroblastoma (NB) model resembling stage 3 NB with thoracic localization has been set up by intramediastinal injection of tumor cells. Two NB cell lines, the murine Neuro2a, and the hybrid NXS2, have been injected in A/J mice. In vivo tumor growth and dissemination have been assessed by macroscopic and microscopic histological analysis performed at different times post injection. Tumor cell localization and growth patterns were compared to those obtained by i.v. and r.p. injections. The results indicated that in the thoracic model both tumor cell lines grow rapidly as huge tumor masses but do not metastatize to distant organs. This new model may be relevant for testing the efficacy of novel immunotherapeutic strategies for poor prognosis NB patients with localized disease.