NLRP3 MODULATES THE INFLAMMATORY RESPONSE IN GRAM-NEGATIVE BACTERIAL INFECTION

Perrella A. NLRP3 modulates the inflammatory response in Gram-negative bacterial infection. International Journal of Infection. 2026;10(1):21-22.

A. Perrella*

Emerging Infectious Disease and High Contagiousness Unit, Cotugno-AORN Ospedali dei Colli, 80131 Naples, Italy.

*Correspondence to:
Alessandro Perrella, MD, PhD,
Emerging Infectious Disease and High Contagiousness Unit,
Cotugno-AORN Ospedali dei Colli,
80131 Naples, Italy.
e-mail: Alessandro.perrella@ospedalideicolli.it

Received: 27 February, 2026 Accepted: 14 April, 2026

ISSN 3103-6678 [online] Copyright 2026 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

KEYWORDS: NOD-like receptor family pyrin domain-containing 3, NLRP3, inflammation, Gram-negative bacteria, infection

INTRODUCTION

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) complex is an important molecule in the innate immune system and plays a key role in regulating inflammation. NLRP3 is an intracellular sensor that recognizes danger signals (PAMPs and DAMPs) and is involved in Gram-negative bacterial infections (1). NLRP3 mediates lipopolysaccharide (LPS) in infection by Gram-negative bacteria, resulting in ionic changes such as K⁺ efflux and cellular damage.

DISCUSSION

Activated NLRP3 forms a complex called the NLRP3 inflammasome, which assembles with other proteins, such as procaspase-1, leading to the activation of caspase-1 (2). The caspase-1 protease belongs to the caspase family and is a key enzyme in inflammatory processes and apoptosis. Activated caspase-1 activates inflammatory cytokines and transforms pro-IL-1β and IL-18 from inactive forms to active mature IL-1β and IL-18 (3).

IL-1β and IL-18 are highly inflammatory cytokines that recruit immune cells and induce pyroptosis, a highly inflammatory form of programmed cell death that is activated primarily in response to microbial infection or cellular damage. Pyroptosis causes rupture of the plasma membrane and the release of pro-inflammatory cellular mediators such as IL-1β and IL-18, which are cytokines with chemotactic power on immune cells (4). This process is beneficial to the body in the event of an infection, as it mobilizes immune cells to fight and eliminate microorganisms such as bacteria and viruses. Pyroptosis helps remove immune cells, preventing them from serving as reservoirs for microorganisms. However, even after pyroptosis, cells still implement survival strategies, such as repairing plasma membranes and/or preventing proteins from polymerizing and causing damage. A better understanding of the stages of cell death is very important for the development of new therapeutic strategies against inflammation.

The NLRP3 inflammasome complex, IL-1β, and IL-18 are very important in the innate inflammatory response. The cytosolic multiprotein NLRP3 inflammasome functions as a danger sensor and includes procaspase-1. NLRP3 is activated in response to PAMPs, such as bacteria and viruses, and DAMPs, including extracellular ATP, urate crystals, reactive oxygen species (ROS), and cell damage (5). Activation leads to a biochemical cascade that produces the transcription factor NF-κB, with increased synthesis of NLRP3 and inactive forms of cytokines such as pro-IL-1β and pro-IL-18. NLRP3 oligomerizes and recruits procaspase-1. Pro-caspase becomes a caspase and cleaves pro-IL-1β, which becomes active IL-1β, and pro-IL-18, which becomes active IL-18, cytokines that promote a potent inflammatory response. Gram-negative bacteria, such as E. coli, activate NLRP3 primarily through LPS, which acts as a primer. This leads to the recruitment of immune cells and elimination of the pathogen.

CONCLUSIONS

In conclusion, NLRP3 is like an “alarm sensor,” but when overactivated, it can cause excessive inflammation, and contribute to sepsis and tissue damage. Therefore, NLRP3 must be finely regulated to avoid unwanted side effects. The role of NLRP3 in inflammatory pathology is still not fully understood. Filling this gap is crucial, as inflammation drives most human diseases.

Conflict of interest

The author declares that they have no conflict of interest.

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