ATP Induces IL-1β Secretion in Neisseria gonorrhoeae-Infected Human Macrophages by a Mechanism Not Related to the NLRP3/ASC/Caspase-1 Axis.

Killen García,Alejandro Escobar,Pablo Mendoza,Paula I Rodas,Caroll Beltran,Gisselle Escobar,Sergio Arancibia,Claudio Acuña-Castillo,Claudio Perez,Rolando Vernal

doi:10.1155/2016/1258504

Abstract

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-1β secretion of infected human monocyte-derived macrophages (MDM). Here, we investigate the role of adenosine triphosphate (ATP) in production and release of IL-1β in Ngo-infected MDM. We found that the exposure of Ngo-infected MDM to ATP increases IL-1β levels 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-1β with a distinctive intracellular pattern of distribution. Collectively, these data demonstrate that ATP induces IL-1β secretion 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.

Highlights

Neisseria gonorrhoeae (Ngo) or gonococcus, a Gram-negative diplococcus, is the etiological agent of the sexually transmitted bacterial infection (STI) gonorrhoea
Previous findings of our laboratory showed that IL-1β present in supernatants from Ngo- infected macrophages at different multiplicity of infection (MOI) was not significantly different from nonstimulated monocyte-derived macrophages (MDM) [15]
IL-1β secretion by macrophages exposed to LPS was much more than IL-1β secreted by Ngo-infected macrophages

Summary

Introduction

Neisseria gonorrhoeae (Ngo) or gonococcus, a Gram-negative diplococcus, is the etiological agent of the sexually transmitted bacterial infection (STI) gonorrhoea. Clinical data indicates that previous gonococcal infections do not improve immune response in patients with reinfection, which suggest that immunological memory is not induced by gonococcus [2]. Since the ineffective immune response against gonococcus is multifactorial, it has been hypothesized that it could be the sum of different mechanisms. Ngo has several mechanisms for evading complement-mediated defences, such as LOS sialylation [8] and binding of PorB molecules to the complement cascade inhibitors factor H and complement factor 4b-binding protein (C4BP) [9]

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Conclusion