ATP Induces IL-1βSecretion inNeisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis.
Neisseria gonorrhoeae(Ngo) has developed multiple immune evasion mechanisms involving the innate and adaptive immune responses. Recent findings have reported that Ngo reduces the IL-1βsecretion of infected human monocyte-derived macrophages (MDM). Here, we investigate the role of adenosine triphosphate (ATP) in production and release of IL-1βin Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1βlevels about ten times compared with unexposed Ngo-infected MDM (P< 0.01). However, we did not observe any changes in inflammasome transcriptional activation of speck-like protein containing a caspase recruitment domain (CARD) (ASC,P> 0.05) and caspase-1 (CASP1,P> 0.05). In addition, ATP was not able to modify caspase-1 activity in Ngo-infected MDM but was able to increase pyroptosis (P> 0.01). Notably ATP treatment defined an increase of positive staining for IL-1βwith a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1βsecretion by a mechanism not related to the NLRP3/ASC/caspase-1 axis and likely is acting at the level of vesicle trafficking or pore formation.
Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago, Chile.
Killen
K
García
Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago, Chile.
Gisselle
G
Escobar
Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago, Chile.
Pablo
P
Mendoza
Departamento de Gastroenterología, Hospital Clínico de la Universidad de Chile, Santiago, Chile.
Caroll
C
Beltran
Banco de Sangre, Hospital Clínico de la Universidad de Chile, Santiago, Chile.
Claudio
C
Perez
Investigación y Desarrollo, Laboratorio Centrovet, Santiago, Chile.
Sergio
0000-0002-3421-2920
S
Arancibia
Departamento de Odontología Conservadora, Facultad de Odontología, Universidad de Chile, Santiago, Chile; Unidad de Odontología, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago, Chile.
Rolando
R
Vernal
Center for Integrative Medicine and Innovative Science, Facultad de Medicina, Universidad Andrés Bello, Santiago, Chile.
Paula I
0000-0002-8071-1229
PI
Rodas
Laboratorio de Inmunología, Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago, Chile.
Claudio
C
Acuña-Castillo
Instituto de Investigación en Ciencias Odontológicas, Facultad de Odontología, Universidad de Chile, Santiago, Chile.
Alejandro
0000-0002-1587-4179
A
Escobar
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism* / Q000382:microbiology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism*; D009344:Neisseria gonorrhoeae / Q000472:pathogenicity*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter; D000255:Adenosine Triphosphate; D020169:Caspases