IN BACTERIAL INFECTIONS, NEUTROPHIL RECEPTORS DETECT AND RESPOND TO PATHOGENS

Caraffa Al, Caccianiga G. In bacterial infections, neutrophil receptors detect and respond to pathogens. International Journal of Infection. 2022;6(1):1-4

Al. Caraffa¹ and G. Caccianiga^2*

¹ School of Pharmacy, University of Camerino, Camerino, Italy;
² School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.

*Correspondence to:
Gianluigi Caccianiga,
School of Medicine and Surgery,
University of Milano-Bicocca,
20900 Monza, Italy.
e-mail: p.caccianiga@campus.unimib.it

Received: 04 December, 2021 Accepted: 12 February, 2022

ISSN 1972-6945 [online] Copyright 2022 © 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.

ABSTRACT

Neutrophils are the first immune cells that intervene after bacterial infection. These cells are the first line of defense in combatting infection by responding to and neutralizing pathogens. They have various receptors such as toll-like receptors (TLRs), NOD-like receptors (NLRs), Fc receptors (complement receptors (CRs)), pattern recognition receptors (PRRs), adhesion receptors, scavenger receptors, and chemokine/cytokine receptors, which are important for binding microorganisms. After neutrophil receptor binding, signaling cascades are activated which lead to gene expression changes that produce neutrophil activation. Then, reactive oxygen species (ROS) are produced which are toxic to bacteria. Additionally, neutrophils can produce proteases and antimicrobial peptides which break down bacterial cell walls and membranes, protecting the body from infection.

KEYWORDS: infection, neutrophil, receptor, bacteria, pathogen, immunity, microbe

INTRODUCTION

Bacterial infections occur when harmful bacteria invade and multiply within the host body, leading to a range of diseases. These infections can trigger immune responses, including the activation of neutrophils, which are a type of white blood cell and are among the first responders to microbial infection (1). They are part of the innate immune system and play a crucial role in defending against bacterial infections. Neutrophils are the first line of defense against infections and are highly effective at responding to and neutralizing pathogens (2).

DISCUSSION

Neutrophils perform various functions which include phagocytosis (the engulfment and digestion of pathogens and debris) (3), degranulation (the release of antimicrobial peptides and enzymes from granules to destroy pathogens) (4), the creation of neutrophil extracellular traps (NETs) (by expelling a web of DNA and antimicrobial proteins to trap and kill pathogens extracellularly) (4), and the production of cytokines that modulate the immune response and recruit other immune cells (5).

Receptors on the surface of neutrophils and other immune cells recognize and bind to specific molecules (ligands) on bacteria. This recognition is crucial for initiating an immune response. Neutrophils have various receptors on their surface that help them recognize, bind to, and respond to pathogens. Some key receptors that are found on neutrophils include toll-like receptors (TLRs), NOD-like receptors (NLRs), Fc receptors (complement receptors (CRs)), pattern recognition receptors (PRRs), adhesion receptors, scavenger receptors, and chemokine/cytokine receptors (6) (Table I).

Table I. Some key neutrophil receptors that play a role in infection.

TLRs recognize pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) on bacterial surfaces (7). NLRs detect intracellular bacterial components, and Fc receptors bind to antibodies that are attached to bacteria, marking them for destruction (8).

Fc Receptors bind to the Fc region of antibodies that are attached to pathogens, facilitating phagocytosis and antibody-dependent cellular cytotoxicity (9). Fc gamma receptors (FcγR) bind to IgG antibodies and include subtypes like FcγRI, FcγRII, and FcγRIII, while Fc alpha receptors (FcαR) bind to IgA antibodies (10).

CRs recognize complement-coated pathogens, enhancing phagocytosis and inflammatory responses (11). CR1 (CD35) binds to C3b and C4b complement fragments. CR3 (CD11b/CD18, also known as Mac-1) binds to iC3b, a breakdown product of C3b. CR4 (CD11c/CD18) also interacts with iC3b and other complement fragments (12).

PRRs recognize PAMPs and damage-associated molecular patterns (DAMPs). TLRs recognize components of microbial pathogens, such as bacterial LPS (TLR4) and flagellin (TLR5) (13,14). NLRs detect intracellular pathogens and initiate inflammatory responses (7). C-type lectin receptors (CLRs) bind to carbohydrate structures on the surfaces of pathogens (15).

Adhesion receptors mediate the adhesion of neutrophils to the endothelium and their transmigration into tissues (16). Integrins, such as LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18), interact with intercellular adhesion molecules (ICAMs) on endothelial cells (17,18). Selectins include L-selectin (CD62L), which mediates initial weak adhesion to the endothelium (19).

Scavenger receptors recognize and bind to a variety of ligands, including modified low-density lipoproteins (LDL) and microbial products. Scavenger receptor-A (SR-A) binds to a variety of polyanionic ligands, while CD36 binds to oxidized LDL and apoptotic cells (20).

Chemokine receptors guide neutrophils to the site of infection or inflammation by detecting chemokines. The receptors CXCR1 and CXCR2 bind to chemokines such as IL-8, which is crucial for neutrophil chemotaxis, and CCR1 and CCR2 respond to other chemokines involved in the recruitment of neutrophils (21).

The interaction between bacterial components and neutrophil receptors involves complex biochemical pathways such as chemotaxis, phagocytosis, degranulation and NETosis. In chemotaxis, neutrophils migrate towards the site of infection in response to chemical signals (chemokines) (22). During phagocytosis, neutrophils engulf and digest bacteria through a process facilitated by receptors such as TLRs and Fc receptors (6). Following phagocytosis there is degranulation, in which antimicrobial substances that destroy bacteria are released from neutrophil granules. During the process of NETosis, NETs are released, which are networks of extracellular fibers composed of DNA and antimicrobial proteins that trap and kill bacteria (23).

Upon receptor binding, signaling cascades are activated (e.g., MAPK, NF-κB) that lead to gene expression changes necessary for neutrophil activation. An oxidative burst follows, with the production of reactive oxygen species (ROS) that are toxic to bacteria. Neutrophils can also produce proteases and antimicrobial peptides, enzymes and peptides that break down bacterial cell walls and membranes.

CONCLUSIONS

Neutrophils are equipped with a diverse array of receptors that enable them to detect and respond to pathogens effectively, thus they play a critical role in the body’s defense mechanisms. In bacterial infections, neutrophils use various receptors to detect and respond to pathogens through intricate molecular and biochemical processes. These responses involve a coordinated effort to locate, identify, and destroy bacterial invaders.

Conflict of interest

The authors declare that they have no conflict of interest.

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