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The Multifunctional Role of Lysozyme in the Human Body and Immune System

Lysozyme, a naturally occurring enzyme present in numerous bodily fluids and tissues, plays a pivotal role in maintaining homeostasis and defending the human body against microbial threats. Known predominantly for its antimicrobial activity, particularly against Gram-positive bacteria, lysozyme is increasingly recognized for a broader range of biological functions, including immunomodulation, inflammation regulation, tissue remodeling, and wound healing.

Explore the structural biology of lysozyme with Creative Enzymes, and its distribution throughout the body, its multifaceted role in immune defense, and its significance in health and disease.

Introduction

The human immune system consists of a complex network of organs, cells, and molecules designed to identify and neutralize potentially harmful invaders such as bacteria, viruses, fungi, and parasites. Among its many defense tools, lysozyme occupies a unique position as one of the most ancient and conserved components of innate immunity.

First discovered by Sir Alexander Fleming in 1922, lysozyme was initially noted for its bacteriolytic effects. Since then, extensive research has illuminated its broader biological roles, including its involvement in immune modulation, apoptosis, mucosal immunity, and even potential roles in cancer suppression. Understanding the multifunctional nature of lysozyme is crucial for appreciating its significance in physiology and its potential therapeutic applications.

Biochemical Structure and Mechanism of Action

Molecular Structure

Lysozyme is a small globular enzyme composed of 129 amino acids and has a molecular weight of approximately 14.3 kilodaltons. It is categorized within the glycoside hydrolase family 22 (GH22) and exhibits a characteristic α-helix and β-sheet arrangement.

One of the most studied lysozymes is the hen egg-white lysozyme (HEWL), used as a model for structural and enzymatic studies. The active site contains two catalytic residues—typically Glu35 and Asp52—which are essential for the cleavage of glycosidic bonds in peptidoglycan.

Structure of hen egg white lysozyme.Figure 1. Structure of hen egg-white lysozyme. (PDB code: 1DPX)

Enzymatic Mechanism

Lysozyme exerts its antibacterial effect by hydrolyzing the β-1,4-glycosidic bond between N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG), which are key components of the bacterial cell wall peptidoglycan layer. This enzymatic action compromises the structural integrity of bacterial cell walls, leading to osmotic imbalance and eventual lysis, particularly in Gram-positive bacteria.

The reaction catalyzed by lysozyme.Figure 2. The reaction catalyzed by lysozyme. The substrate is bound so that the leaving group oxygen, the 4-OH group of an N-acetylglucosamine (NAG) residue, is protonated as it leaves by the COOH group of Glu 35. (Kirby, 2001)

Tissue Distribution of Lysozyme in the Human Body

Lysozyme's widespread presence across diverse tissues and secretions reflects its critical role as a frontline defender of the human body. It is especially abundant in anatomical regions that interface with the external environment, providing constant surveillance against microbial infiltration.

Secretory Fluids

Lysozyme is secreted into a variety of bodily fluids, acting as a soluble antimicrobial agent.

Cellular Sources

Lysozyme is synthesized and secreted by several cell types, highlighting its integrated function across both innate and adaptive immune compartments.

Lysozyme and Innate Immunity

Lysozyme is a cornerstone molecule of the innate immune system, offering rapid, non-specific responses to microbial invasion.

First-Line Defense Mechanism

Lysozyme represents a classic example of a pattern recognition molecule, capable of identifying structural motifs shared by many microbes, particularly the carbohydrate components of peptidoglycan. This pattern recognition capability allows it to act before adaptive immune responses are mobilized.

When pathogens breach the physical barriers of the skin or mucosa, lysozyme acts as part of a biochemical shield. It is especially effective in nasopharyngeal and gastrointestinal mucosa, where it operates in concert with:

In this biochemical milieu, lysozyme accelerates pathogen lysis and clearance, while its cationic nature helps it interact with negatively charged microbial surfaces, enhancing its antimicrobial efficacy.

Selectivity Toward Microbial Targets

Lysozyme is notably potent against Gram-positive bacteria, whose thick, exposed peptidoglycan layers are readily cleaved. For example, Staphylococcus aureus and Bacillus subtilis are particularly susceptible.

However, Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa, possess an outer membrane that protects their peptidoglycan from enzymatic attack. Nevertheless, lysozyme can still target these organisms when:

Thus, lysozyme is not restricted to Gram-positive organisms, especially when functioning as part of a broader immune response.

Two mechanisms by which lysozyme kills bacteria.Figure 3. Lysozyme can kill bacteria through 2 mechanisms. (A) Peptidoglycan (PG) monomers—NAG linked to NAM with a peptide stem—are assembled into the cell wall by glycosyltransferases (green). (B) Lysozyme cleaves the β-1,4 bond between NAM and NAG, disrupting PG and causing cell lysis. (C) Independently, lysozyme's cationic properties may form pores (red) in membranes, leading to cell death. (Ragland and Criss, 2017)

Immunomodulatory Roles of Lysozyme

Beyond its role as a bacteriolytic enzyme, lysozyme has profound effects on immune cell behavior, cytokine signaling, and tissue homeostasis.

Modulation of Cytokine Production

Lysozyme can influence the cytokine milieu in inflamed tissues. When taken up by antigen-presenting cells such as macrophages or dendritic cells, it can:

Conversely, under conditions of resolved infection or during tissue repair, lysozyme appears to boost IL-10 and TGF-β, both of which are anti-inflammatory cytokines that help restore tissue integrity and suppress further immune activation.

These dual effects highlight lysozyme's role as a context-dependent immunomodulator, rather than merely a microbe-killer.

Lysozyme modulates cytokine production.Figure 4. Lysozyme modulates the immune response. (Ragland and Criss, 2017)

Regulation of Apoptosis and Cell Turnover

Lysozyme can modulate programmed cell death (apoptosis), particularly in epithelial cells and leukocytes. By influencing apoptosis, lysozyme:

Through these mechanisms, lysozyme contributes not only to pathogen elimination but also to the orchestration of tissue repair and immune homeostasis.

Lysozyme in the Gastrointestinal Tract

The gut represents one of the most complex immunological interfaces in the body, and lysozyme plays a central role in maintaining its balance.

Microbiota Homeostasis

In the intestinal lumen, lysozyme helps regulate the composition of the gut microbiome by:

Paneth cells in the small intestine release lysozyme into the crypts of Lieberkühn, protecting the intestinal stem cell niche from microbial invasion.

Dysregulation of this system—whether through genetic mutations in NOD2 or ATG16L1, or environmental triggers—has been implicated in dysbiosis, which can contribute to a variety of conditions, including obesity, metabolic syndrome, and inflammatory bowel disease.

Defense Against Pathogens

During infections by enteric pathogens like Salmonella enterica, Clostridium difficile, or Listeria monocytogenes, lysozyme is rapidly secreted by Paneth cells and infiltrating neutrophils. It works in tandem with antimicrobial peptides and immunoglobulins to neutralize the threat before pathogens can cross the epithelial barrier.

In animal models, lysozyme deficiency has been linked to increased susceptibility to colitis and systemic bacterial translocation, underscoring its indispensable role in intestinal immunity.

Implications in Inflammatory Bowel Disease (IBD)

In Crohn's disease and ulcerative colitis, aberrant lysozyme expression has been documented. It is hypothesized that:

This makes lysozyme a potential biomarker of mucosal immune activation and a target for therapeutic modulation in IBD.

Lysozyme is a potent target for therapeutic modulation in inflammatory bowel disease.Figure 5. Hypothesized model of perpetuated inflammation in inflammatory bowel disease (IBD). (Zigdon and Bel, 2020)

Role in Wound Healing and Tissue Remodeling

Lysozyme is increasingly being recognized for its involvement in non-infectious processes, particularly tissue repair.

Debridement and Antimicrobial Cleansing

In wounds, lysozyme helps remove dead tissue and microbial contaminants. This enzymatic debridement is critical for preparing the wound bed for granulation and re-epithelialization.

Anti-inflammatory Action

By modulating cytokine levels and scavenging reactive oxygen species, lysozyme helps limit the extent and duration of inflammation, reducing the risk of chronic wound formation.

Promotion of Fibroblast Activity

Lysozyme can stimulate fibroblast proliferation and collagen synthesis, essential for extracellular matrix production and wound closure. Its presence enhances angiogenesis and promotes the re-establishment of tissue integrity.

Advanced delivery systems—such as lysozyme-loaded hydrogels, nanofibers, and biodegradable scaffolds—are being explored to optimize its therapeutic potential in wound management.

Phase-transited lysozyme gel.Figure 6. Functions of phase-transited lysozyme gel. (Chen et al., 2022)

Lysozyme and Systemic Inflammation

While lysozyme acts locally at epithelial surfaces, it also plays a role in systemic immune responses.

Acute-Phase Response

In response to systemic infections or trauma, the liver upregulates the production of acute-phase proteins, including lysozyme. Elevated serum lysozyme levels have been observed in conditions such as:

These elevated levels often correlate with bacterial burden and may serve as diagnostic or prognostic markers in clinical settings.

Chronic Inflammatory Conditions

Persistent elevation of lysozyme has been documented in diseases like:

Although not routinely used as a standalone diagnostic tool, serum lysozyme may complement other inflammatory markers like CRP and ESR in certain clinical contexts.

Recommended Products

Catalog Product Name Source Price
NATE-4728 Lysozyme from Chicken Egg White Chicken egg white Inquiry
NATE-0433 Native Human Lysozyme Human neutrophils
CEFX-025 Human Sputum Lysozyme (Sterilized) Leukocytes in septic human sputum
NATE-0432 Lysozyme (Food Grade) Chicken egg white
NATE-0434 Lysozyme from Human, Recombinant Rice
NATE-1455 Lysozyme 23A from Bacillus subtilis, Recombinant E. coli
NATE-1456 Lysozyme 25A from Streptococcus pneumoniae, Recombinant E. coli

Lysozyme, long regarded as a simple antimicrobial enzyme, is increasingly recognized as a multifunctional mediator within the human body. Its diverse roles in mucosal defense, immune regulation, tissue repair, and inflammation underscore its physiological importance and therapeutic potential. In an era of rising antibiotic resistance and chronic inflammatory diseases, lysozyme represents a compelling candidate for novel therapeutic strategies. Continued research into its mechanisms, regulation, and engineering may yield transformative advances in immunology, infectious disease, and regenerative medicine.

At Creative Enzymes, we provide premium lysozyme products designed to meet the highest quality standards for both research and therapeutic use. Contact us with any questions or inquiries.

References:

  1. Chen J, Xu M, Wang L, et al. Converting lysozyme to hydrogel: A multifunctional wound dressing that is more than antibacterial. Colloids and Surfaces B: Biointerfaces. 2022;219:112854. doi:10.1016/j.colsurfb.2022.112854
  2. Kirby AJ. The lysozyme mechanism sorted — after 50 years. Nat Struct Biol. 2001;8(9):737-739. doi:10.1038/nsb0901-737
  3. Ragland SA, Criss AK. From bacterial killing to immune modulation: Recent insights into the functions of lysozyme. Bliska JB, ed. PLoS Pathog. 2017;13(9):e1006512. doi:10.1371/journal.ppat.1006512
  4. Zigdon M, Bel S. Lysozyme: a double-edged sword in the intestine. Trends in Immunology. 2020;41(12):1054-1056. doi:10.1016/j.it.2020.10.010