HOW YOUR BODY KILLS LYME DISEASE AND BARTONELLA
TOP VETERAN AUTHOR GIVES EXAMPLES

25 ways the mammalian body kills or suppresses bacteria

1. Neutrophil phagocytosis

Neutrophils recognize, engulf and destroy bacteria inside phagosomes. After engulfment, the phagosome undergoes maturation and acquires enzymes and antimicrobial machinery capable of killing the organism.

Neutrophils are among the fastest and most important antibacterial cells in mammals.

Reference:
Flannagan RS, Cosío G, Grinstein S. Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nature Reviews Microbiology. 2009;7:355–366.

2. Macrophage phagocytosis

Macrophages engulf bacteria and deliver them into specialized intracellular compartments where they are exposed to:

• reactive oxygen species
• reactive nitrogen species
• lysosomal enzymes
• acidic conditions
• antimicrobial peptides
• nutrient deprivation

Macrophages can therefore function as both bacterial scavengers and killing cells.

Reference:
Sweet MJ, Ramnath D, Singhal A, et al. Inducible antibacterial responses in macrophages. Nature Reviews Immunology. 2025;25:92–107.

3. Complement-mediated killing

The complement system can directly kill susceptible bacteria through the membrane attack complex (MAC; C5b–C9).

Complement also coats bacteria with C3 fragments, making them dramatically easier for phagocytes to recognize and ingest.

Reference:
Innate immunity: current understandings and future perspectives. Signal Transduction and Targeted Therapy. 2026.

4. Complement opsonization

Complement doesn’t always kill bacteria directly.

C3b and related complement fragments act as opsonins, essentially putting an immunological “eat me” signal on the bacterial surface.

Neutrophils and macrophages possess complement receptors that recognize these molecules.

This greatly increases opsonophagocytosis.

Reference:
Innate immunity: current understandings and future perspectives. Signal Transduction and Targeted Therapy. 2026.

5. Antibodies

Antibodies can eliminate bacteria through several mechanisms:

• neutralizing bacterial toxins
• blocking bacterial attachment
• agglutinating organisms
• activating complement
• coating bacteria for phagocytosis
• promoting antibody-dependent cellular killing

IgG is particularly important in systemic antibacterial defense, while IgA is extremely important at mucosal surfaces.

Reference:
Lu LL, Suscovich TJ, Fortune SM, Alter G. Beyond binding: antibody effector functions in infectious diseases. Nature Reviews Immunology. 2018;18:46–61.

6. Lysozyme

Lysozyme is an antimicrobial enzyme found in:

• tears
• saliva
• mucus
• breast milk
• airway secretions
• neutrophil granules

It cleaves bonds in peptidoglycan, a structural component of bacterial cell walls.

It is particularly effective against many Gram-positive bacteria.

Reference:
Ragland SA, Criss AK. From bacterial killing to immune modulation: recent insights into the functions of lysozyme. PLoS Pathogens. 2017;13:e1006512.

7. Lactoferrin

Lactoferrin is an iron-binding protein found prominently in mucosal secretions and neutrophil granules.

It deprives bacteria of iron and can also interact directly with bacterial surfaces.

This is an important component of nutritional immunity.

Reference:
Drago-Serrano ME, de la Garza-Amaya M, Luna JS, Campos-Rodríguez R. Lactoferrin-lipopolysaccharide interaction: molecular basis and clinical implications. Biometals. 2012;25:143–157.

8. Defensins

Defensins are small antimicrobial peptides that can insert into microbial membranes and disrupt them.

Mammals produce several families, including:

• α-defensins
• β-defensins

They are important at epithelial surfaces and in leukocytes.

Reference:
Ganz T. Defensins: antimicrobial peptides of innate immunity. Nature Reviews Immunology. 2003;3:710–720.

9. Cathelicidins

Cathelicidins are another major family of mammalian antimicrobial peptides.

The best-known human cathelicidin is LL-37.

These peptides can disrupt bacterial membranes and can also influence immune-cell recruitment and inflammatory responses.

Reference:
Zanetti M. Cathelicidins, multifunctional peptides of the innate immunity. Journal of Leukocyte Biology. 2004;75:39–48.

10. Reactive oxygen species — oxidative burst

When neutrophils and macrophages engulf bacteria, NADPH oxidase can generate a powerful oxidative burst.

This produces reactive oxygen species including:

• superoxide
• hydrogen peroxide
• downstream oxidants

These molecules damage bacterial proteins, membranes and DNA.

Reference:
Flannagan RS, Cosío G, Grinstein S. Nature Reviews Microbiology. 2009;7:355–366.

11. Myeloperoxidase

Neutrophils contain the enzyme myeloperoxidase (MPO).

MPO uses hydrogen peroxide and chloride to generate hypochlorous acid (HOCl), a highly reactive antimicrobial oxidant.

This is one of the most powerful chemical killing mechanisms inside neutrophil phagosomes.

Reference:
Klebanoff SJ. Myeloperoxidase: friend and foe. Journal of Leukocyte Biology. 2005;77:598–625.

12. Reactive nitrogen species

Macrophages can produce nitric oxide (NO) and related reactive nitrogen intermediates.

These molecules can damage bacterial proteins, enzymes and metabolic pathways.

This mechanism is especially important against some intracellular pathogens.

Reference:
MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annual Review of Immunology. 1997;15:323–350.

13. Neutrophil extracellular traps — NETs

Neutrophils can release networks of DNA and antimicrobial proteins called NETs.

NETs can trap bacteria and expose them to concentrated antimicrobial proteins and enzymes.

NET formation is particularly relevant for organisms that are difficult to contain through ordinary phagocytosis.

Reference:
Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004;303:1532–1535.

14. Acidification of the phagosome

After a bacterium is engulfed, the phagosome becomes progressively more acidic.

This:

• activates antimicrobial enzymes
• damages bacterial physiology
• facilitates lysosomal killing
• creates an unfavorable environment for bacterial survival

Phagosome maturation is therefore an important component of killing.

Reference:
Flannagan RS, Cosío G, Grinstein S. Nature Reviews Microbiology. 2009;7:355–366.

15. Lysosomal enzymes

Phagocytes fuse bacteria-containing compartments with lysosomes.

The resulting phagolysosome contains numerous destructive enzymes, including:

• proteases
• lipases
• nucleases
• glycosidases
• other hydrolytic enzymes

These enzymatically dismantle bacterial structures.

Reference:
Flannagan RS, Cosío G, Grinstein S. Nature Reviews Microbiology. 2009;7:355–366.

16. Nutritional immunity — iron sequestration

The body deliberately makes iron difficult for bacteria to obtain.

Major players include:

• transferrin
• lactoferrin
• ferritin
• hepcidin
• ferroportin
• haptoglobin
• hemopexin

Since many pathogenic bacteria require iron for critical metabolic processes, restricting iron can substantially limit their growth.

Reference:
Frost JN, Drakesmith H. Iron and the immune system. Nature Reviews Immunology. 2025;25:885–899.

17. Zinc and manganese sequestration

The mammalian immune system also restricts bacterial access to zinc and manganese.

S100-family proteins, particularly proteins such as calprotectin, can bind these metals.

This deprives bacteria of essential cofactors.

Reference:
Murdoch CC, Skaar EP. Nutritional immunity: the battle for nutrient metals at the host–pathogen interface. Nature Reviews Microbiology. 2022;20:657–670.

18. Metal intoxication

Interestingly, mammals don’t only starve bacteria of metals.

They can sometimes deliberately expose bacteria to toxic concentrations of metals such as:

• copper
• zinc
• manganese

This can damage bacterial proteins and interfere with metabolism.

Thus the immune system uses both:

metal starvation + metal poisoning.

Reference:
Hood MI, Skaar EP. Nutritional immunity: transition metals at the pathogen–host interface. Nature Reviews Microbiology. 2012;10:525–537.

19. Fever

An increase in body temperature can make the environment less favorable for some pathogens while simultaneously altering immune-cell function.

Fever is therefore part of the systemic host response to infection.

However, fever is not universally bactericidal, and excessively high temperatures are harmful.

Reference:
Evans SS, Repasky EA, Fisher DT. Fever and the thermal regulation of immunity: the immune system feels the heat. Nature Reviews Immunology. 2015;15:335–349.

20. Mucus trapping and mucociliary clearance

The respiratory tract uses mucus to trap bacteria.

Cilia then move mucus toward the throat, where it can be swallowed or expelled.

This prevents bacteria from reaching deeper tissues in the first place.

Reference:
Bustamante-Marin XM, Ostrowski LE. Cilia and mucociliary clearance. Cold Spring Harbor Perspectives in Biology. 2017;9:a028241.

21. Gastric acid

The extremely acidic environment of the stomach kills or severely damages many microorganisms before they reach the intestine.

This is one of the body’s most important pre-infection barriers.

Reference:
Martinsen TC, Bergh K, Waldum HL. Gastric juice: a barrier against infectious diseases. Basic & Clinical Pharmacology & Toxicology. 2005;96:94–102.

22. Skin barrier + antimicrobial surface chemistry

The skin prevents bacterial entry through:

• physical keratinized barriers
• tight cellular junctions
• acidic surface conditions
• antimicrobial peptides
• sebum
• resident microbiota

Thus the body frequently prevents bacteria from reaching viable tissue rather than killing them after invasion.

Reference:
Pasparakis M, Haase I, Nestle FO. Mechanisms regulating skin immunity and inflammation. Nature Reviews Immunology. 2014;14:289–301.

23. Intestinal microbiota — colonization resistance

Normal mammalian microbiota can suppress invading bacteria by:

• consuming nutrients
• occupying attachment sites
• producing bacteriocins
• producing short-chain fatty acids
• modifying the local environment
• stimulating host antimicrobial defenses

This is called colonization resistance.

Reference:
Buffie CG, Pamer EG. Microbiota-mediated colonization resistance against intestinal pathogens. Nature Reviews Immunology. 2013;13:790–801.

24. Autophagy and xenophagy

Cells can identify and deliver some intracellular bacteria to autophagic machinery.

This process—often called xenophagy—can restrict or destroy intracellular pathogens.

Autophagy can also cooperate with inflammatory and lysosomal pathways.

Reference:
Deretic V, Saitoh T, Akira S. Autophagy in infection, inflammation and immunity. Nature Reviews Immunology. 2013;13:722–737.

25. Inflammasomes and pyroptosis

Some intracellular bacterial infections activate inflammasomes, which can activate inflammatory caspases and trigger pyroptosis, an inflammatory form of programmed cell death.

This can:

• destroy the infected cellular niche
• expose bacteria to immune attack
• recruit additional immune cells
• release inflammatory mediators

It is particularly important against intracellular bacteria.

Reference:
Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nature Reviews Immunology. 2016;16:407–420.

The body’s antibacterial system can be viewed as 6 layers

The 25 mechanisms above aren’t isolated. They work as a coordinated system:

Layer 1 — Keep bacteria out

Skin → mucus → cilia → stomach acid → normal microbiota

Layer 2 — Detect them

TLRs → NOD receptors → other pattern-recognition receptors

Layer 3 — Tag and trap them

Complement → antibodies → mucus → NETs

Layer 4 — Eat them

Neutrophils → macrophages → phagocytosis

Layer 5 — Chemically destroy them

ROS → MPO/HOCl → nitric oxide → antimicrobial peptides → lysosomal enzymes

Layer 6 — Starve or poison them

Iron sequestration → zinc/manganese sequestration → copper/metal intoxication

This is why simply asking “what boosts white blood cells?” misses much of the biology. The mammalian immune system doesn’t rely on one antibacterial mechanism—it uses multiple overlapping mechanisms with different vulnerabilities and different bacterial targets.