IMMUNOLOGICAL AND BIOCHEMICAL MECHANISMS OF BACTERIAL TRACHEITIS

Robuffo I. Immunological and biochemical mechanisms of bacterial tracheitis. International Journal of Infection. 2022;6(2):64-67

I. Robuffo^*

Institute of Molecular Genetics, National Research Council, Section of Chieti, Chieti, Italy.

*Correspondence to:
Dr. Iole Robuffo,
Institute of Molecular Genetics,
National Research Council,
Section of Chieti,
66100 Chieti, Italy.
e-mail: iole.robuffo@cnr.it

Received: 07 April, 2022 Accepted: 23 June, 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.

KEYWORDS: bacterial tracheitis, immunology, pathogenesis, infection, bacteria

INTRODUCTION

Bacterial tracheitis, also known as bacterial croup or bacterial laryngotracheobronchitis, is an acute infection of the trachea caused by various bacterial pathogens. This condition primarily affects young children and can lead to severe airway obstruction and respiratory distress. Understanding the molecular mechanisms underlying bacterial tracheitis is crucial for developing effective treatments and preventive measures. This paper explores the pathogenesis, bacterial virulence factors, host immune responses, and potential therapeutic targets associated with bacterial tracheitis.

DISCUSSION

Bacterial tracheitis typically begins with a viral upper respiratory infection that disrupts the normal mucosal barriers and ciliary function of the respiratory tract. This disruption allows bacteria to adhere to and colonize the tracheal epithelium. Common bacterial pathogens include Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis (1). These bacteria possess various adhesins that facilitate attachment to epithelial cells. For instance, S. aureus expresses fibronectin-binding proteins (FnBPs) and clumping factors (ClfA and ClfB), which bind to host extracellular matrix components such as fibronectin and fibrinogen, respectively (2). Bacterial tracheitis infection includes different pathogenetic steps which are outlined below (Table I).

Table I. Progression of the pathogenesis of bacterial tracheitis.

Once attached, bacteria can invade the epithelial cells and evade the host immune system. S. aureus secretes several toxins and enzymes, including alpha-toxin, leukocidins, and proteases, which damage epithelial cells and disrupt the integrity of the mucosal barrier (3). This facilitates bacterial invasion and dissemination. Additionally, H. influenzae and M. catarrhalis produce biofilms, complex communities of bacteria embedded in a self-produced extracellular matrix (4). Biofilms protect bacteria from phagocytosis and antibiotic treatment, contributing to chronic and recurrent infections.

Virulence factors play a critical role in the pathogenesis of bacterial tracheitis. Exotoxins, such as S. aureus alpha-toxin, are cytolytic toxins that form pores in the host cell membranes, leading to cell lysis and death (5). Leukocidins, another group of toxins produced by S. aureus, specifically target and kill leukocytes, impairing the host’s immune response (6). Additionally, bacterial proteases degrade host proteins, including immunoglobulins and complement proteins, further undermining immune defenses.

Adhesins and surface proteins are essential for bacterial attachment and colonization. In H. influenzae, the Haemophilus adhesion and penetration protein (Hap) and the H. influenzae type b antigen (Hib) are key adhesins that mediate attachment to respiratory epithelial cells (7). Similarly, M. catarrhalis expresses the ubiquitous surface proteins A1 and A2 (UspA1 and UspA2), which bind to host epithelial cells and immune molecules like immunoglobulin D (IgD) (8).

The host immune response to bacterial tracheitis involves both innate and adaptive mechanisms. The innate immune response is the first line of defense and includes physical barriers, cellular responses, and soluble factors. The mucociliary escalator, consisting of ciliated epithelial cells and mucus, traps and removes inhaled pathogens. However, when this system is compromised, innate immune cells such as neutrophils, macrophages, and dendritic cells play a crucial role. These cells recognize pathogen-associated molecular patterns (PAMPs) via pattern recognition receptors (PRRs) like toll-like receptors (TLRs). For instance, TLR4 recognizes lipopolysaccharide (LPS) from gram-negative bacteria, leading to the activation of nuclear factor-kappa B (NF-κB) and the production of pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor (TNF) (9).

The adaptive immune response is also critical in controlling bacterial tracheitis. B cells produce specific antibodies that neutralize bacterial toxins and promote opsonization and phagocytosis. T cells, particularly CD4+ helper T cells, secrete cytokines that enhance the antimicrobial functions of phagocytes and stimulate B cell antibody production. CD8+ cytotoxic T cells can directly kill infected cells, limiting the spread of intracellular pathogens. The interplay between the innate and adaptive immune responses is essential for effective clearance of the infection and prevention of recurrence.

The cornerstone of bacterial tracheitis treatment is antibiotic therapy. The choice of antibiotics depends on the causative pathogen and its susceptibility profile. Empirical treatment often includes broad-spectrum antibiotics such as ceftriaxone, cefotaxime, or clindamycin until the specific pathogen is identified. For S. aureus infections, particularly methicillin-resistant S. aureus (MRSA), vancomycin or linezolid may be necessary. However, the increasing prevalence of antibiotic resistance highlights the need for alternative therapeutic strategies.

Targeting bacterial virulence factors represents a promising approach to treating bacterial tracheitis. Inhibitors of bacterial adhesins, exotoxins, and biofilm formation can potentially reduce bacterial pathogenicity without exerting selective pressure for resistance. For instance, monoclonal antibodies against S. aureus alpha-toxin have shown efficacy in neutralizing the toxin’s activity and protecting against infection in preclinical models (10). Similarly, small molecules that disrupt biofilm formation or enhance biofilm dispersion could improve the efficacy of antibiotic treatment.

Modulating the host immune response is another potential therapeutic strategy. Enhancing the innate immune response through the administration of cytokines or immune stimulants could boost the body’s ability to fight off bacterial infections. For example, granulocyte-macrophage colony-stimulating factor (GM-CSF) has been investigated for its potential to enhance neutrophil function in bacterial infections (11). Additionally, targeting specific inflammatory pathways with anti-inflammatory agents could reduce tissue damage and improve clinical outcomes.

CONCLUSIONS

Bacterial tracheitis is a severe infection of the trachea caused by various bacterial pathogens. Understanding the molecular mechanisms underlying its pathogenesis, including bacterial entry, colonization, virulence factors, and host immune responses, is crucial for developing effective treatments. While antibiotic therapy remains the primary treatment, emerging strategies targeting bacterial virulence factors and modulating the host immune response hold promise for improving outcomes and combating antibiotic resistance. Continued research into these mechanisms will be essential for advancing the management and prevention of bacterial tracheitis.

Conflict of interest

The author declares that they have no conflict of interest.

REFERENCES

1. Kuo CY, Parikh SR. Bacterial Tracheitis. Pediatrics in Review. 2014;35(11):497-499. doi:https://doi.org/10.1542/pir.35-11-497
2. Speziale P, Pietrocola G. The Multivalent Role of Fibronectin-Binding Proteins A and B (FnBPA and FnBPB) of Staphylococcus aureus in Host Infections. Frontiers in Microbiology. 2020;11. doi:https://doi.org/10.3389/fmicb.2020.02054
3. Pietrocola G, Nobile G, Rindi S, Speziale P. Staphylococcus aureus Manipulates Innate Immunity through Own and Host-Expressed Proteases. Frontiers in Cellular and Infection Microbiology. 2017;7(166). doi:https://doi.org/10.3389/fcimb.2017.00166
4. Armbruster CE, Hong W, Pang B, et al. Indirect Pathogenicity of Haemophilus influenzae and Moraxella catarrhalis in Polymicrobial Otitis Media Occurs via Interspecies Quorum Signaling. McDaniel LS, ed. mBio. 2010;1(3). doi:https://doi.org/10.1128/mbio.00102-10
5. Seilie ES, Bubeck Wardenburg J. Staphylococcus aureus pore-forming toxins: The interface of pathogen and host complexity. Seminars in Cell & Developmental Biology. 2017;72:101-116. doi:https://doi.org/10.1016/j.semcdb.2017.04.003
6. Bennett MR, Thomsen IP. Epidemiological and Clinical Evidence for the Role of Toxins in S. aureus Human Disease. Toxins. 2020;12(6):408. doi:https://doi.org/10.3390/toxins12060408
7. Singh B, Jalalvand F, Mörgelin M, Zipfel P, Blom AM, Riesbeck K. Haemophilus influenzaeprotein E recognizes the C‐terminal domain of vitronectin and modulates the membrane attack complex. Molecular Microbiology. 2011;81(1):80-98. doi:https://doi.org/10.1111/j.1365-2958.2011.07678.x
8. Tan T, Nordström T, Forsgren A, Riesbeck K. The Respiratory Pathogen Moraxella catarrhalis Adheres to Epithelial Cells by Interacting with Fibronectin through Ubiquitous Surface Proteins A1 and A2. The Journal of Infectious Diseases. 2005;192(6):1029-1038. doi:https://doi.org/10.1086/432759
9. Zamyatina A, Heine H. Lipopolysaccharide Recognition in the Crossroads of TLR4 and Caspase-4/11 Mediated Inflammatory Pathways. Frontiers in Immunology. 2020;11. doi:https://doi.org/10.3389/fimmu.2020.585146
10. Mayor A, Chesnay A, Desoubeaux G, Ternant D, Heuzé-Vourc’h N, Sécher T. Therapeutic Antibodies for the Treatment of Respiratory Tract Infections—Current Overview and Perspectives. Vaccines. 2021;9(2):151. doi:https://doi.org/10.3390/vaccines9020151
11. Ballinger MN, Paine R, Serezani CHC, et al. Role of Granulocyte Macrophage Colony-Stimulating Factor during Gram-Negative Lung Infection with Pseudomonas aeruginosa. American Journal of Respiratory Cell and Molecular Biology. 2006;34(6):766-774. doi:https://doi.org/10.1165/rcmb.2005-0246oc