AIM2 inflammasome is associated with disease severity in tegumentary leishmaniasis caused by Leishmania (V.) braziliensis

• Published in: Parasite immunology Vol. 39; no. 7
• Main Authors: Moreira, R. B., Pirmez, C., Oliveira‐Neto, M. P., Aguiar, L. S., Gonçalves, A. J. S., Pereira, L. O. R., Abreu, L., De Oliveira, M. P.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2017
• Subjects: Adult; AIM2; Animals; Beta cells; Cutaneous leishmaniasis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Female; Gene expression; Glucosamine - analogs & derivatives; Glucosamine - therapeutic use; Humans; Inflammasome; Inflammasomes; Interleukin 1; Interleukin-1beta - metabolism; Leishmania (Viannia) braziliensis; Leishmania braziliensis - immunology; leishmaniasis; Leishmaniasis, Cutaneous - drug therapy; Leishmaniasis, Cutaneous - immunology; Leishmaniasis, Cutaneous - parasitology; Leishmaniasis, Mucocutaneous - drug therapy; Leishmaniasis, Mucocutaneous - immunology; Leishmaniasis, Mucocutaneous - parasitology; Male; Metalloendopeptidases - genetics; Metalloendopeptidases - metabolism; Middle Aged; Mucosa; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Parasitic diseases; Polymerase chain reaction; Real-Time Polymerase Chain Reaction; Skin diseases; Tegumentary leishmaniasis; therapy response; Leishmania (Viannia) braziliensis; Inflammasome; AIM2; leishmaniasis; therapy response
• ISSN: 0141-9838; 1365-3024
• DOI: 10.1111/pim.12435

Summary The inflammasome is a multiprotein signalling platform involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated gene and protein expression of the inflammasome molecules AIM2 and NLRP3 in active lesions from patients with L. (V.) braziliensis‐associated tegumentary leishmaniasis (TL) and correlated these findings with the clinical presentations and responses to therapy. Real‐time PCR assays showed a significantly higher AIM2 gene expression in mucosal leishmaniasis (ML) compared with that in cutaneous leishmaniasis (CL). Additionally, AIM2 mRNA expression was significantly higher in lesions from poor responders than in lesions from good responders. In situ protein quantification analyses revealed greater AIM2 expression in ML lesions than in CL lesions. The percentage of AIM2‐producing cells was higher in poor responders than in good responders. Although not quite significant, IL‐1β+ cells were slightly more prominent in poor responders than in good responders. Similar results were observed when patients were evaluated according to clinical form. GP63 immunostaining was identified in all samples, but no significant variation between mucosal and cutaneous lesions was observed. GP63 could be associated with reduced NLRP3 inflammasome expression in CL and ML patients. Taken together, these data demonstrate that AIM2 is an important component of the inflammasome in TL patients and is directly associated with the severity of lesions.