Borrelia: the pathway in the body · Biomarker & Blood Analysis

This page shows the biochemical pathway behind the laboratory value Borrelia antibodies: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Borrelia are spiral-shaped bacteria that ticks transmit while feeding on blood. In the body, immune cells recognise their surface proteins, and B cells form antibodies that can be detected in the blood. With a changeable coat, they partly evade these antibodies.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Borrelia in the tick → Coat is remodelled Regulator RpoS · Blood meal As soon as the tick feeds on blood, temperature, acidity and nutrients in its gut change. Using their own regulator, the bacteria switch their surface proteins: OspA down, OspC up. This lets them leave the tick gut. Source 1, 2↑ supplies The switch makes the bacteria ready to travel: with less OspA they detach from the tick gut, and in animal models they need OspC to settle in the host's skin. The regulator RpoS controls both. observed in studies Source 1, 2
   ⚖ When the balance tips

   too much — Once the switch runs, the bacteria lose their hold in the tick gut and carry OspC, which the host's immune cells and antibodies later recognise as a target.

   too little — If the switch does not happen, for example without the regulator RpoS, the bacteria stay attached to the tick gut with OspA; in animal models such strains do not reach the host.

   observed in studies · Source 1, 2, 4

2. Coat is remodelled → In the salivary gland With their new coat the bacteria detach from the gut wall, cross the tick's body cavity and reach its salivary gland. Depending on the tick species this takes one to two days. The longer the tick feeds, the more arrive. Source 2↑ supplies The migration needs time: only after the blood meal begins do the bacteria multiply and reach the salivary gland. The longer the tick feeds, the more bacteria have arrived there. observed in studies Source 2
   ⚖ When the balance tips

   too much — If the tick feeds for a long time, more bacteria reach the salivary gland and enter the skin with the saliva.

   too little — If the blood meal ends early, the bacteria have often not yet reached the salivary gland; then few or none enter the skin.

   observed in studies · Source 2

3. In the salivary gland → In the skin · Salp15 and others The bacteria enter the skin with the saliva. Proteins from tick saliva, such as Salp15, bind to OspC and dampen the first response of immune cells there. This gives the bacteria time. Source 2, 1↓ depletes Salp15 wraps around OspC like a coat and shields the bacteria; at the same time it dampens T cells and dendritic cells in the skin. This gives the bacteria time to settle. observed in studies Source 2, 1
   ⚖ When the balance tips

   too much — If the saliva contains plenty of Salp15, the bacteria are shielded more strongly, and immune cells and antibodies reach them less well in the skin; in animal models more of them then survive.

   too little — Without shielding by saliva proteins, immune cells recognise the bacteria in the skin earlier; in animal models fewer of them then settle.

   observed in studies · Source 2

4. In the skin → In connective tissue Adhesins DbpA/B · BBK32 Borrelia move through dense tissue in a corkscrew motion using internal flagella. Adhesins such as DbpA/B and BBK32 bind to decorin and fibronectin, building blocks of connective tissue. This lets them spread from the bite site. Source 3↑ supplies Adhesion holds the bacteria in the tissue so that blood and lymph flow do not wash them away; the flagella carry them onward. In this way they spread from the bite site to other tissues. observed in studies Source 3
   ⚖ When the balance tips

   too much — If the adhesins find plenty of decorin, as in skin and joints, more bacteria adhere there; in animal models they then colonise these tissues more densely.

   too little — If adhesins such as DbpA/B are missing, the bacteria adhere less well; in animal models such strains spread less and are cleared more easily.

   observed in studies · Source 3

5. Innate immunity → Antigen presentation Dendritic cells engulf fragments of the bacteria, migrate to the nearest lymph node and present the fragments to T cells there. This starts the targeted response. Source 4, 5↑ supplies The dendritic cell links innate and acquired immunity: in the lymph node it specifically activates the T cells whose receptors match fragments of Borrelia. established physiology Source 4, 5
   ⚖ When the balance tips

   too much — If many dendritic cells bring fragments, more matching T cells are activated, and the response in the lymph node becomes broader.

   too little — If few fragments arrive, few T cells are activated, and the help for B cells is weaker.

   established physiology · Source 4, 5

6. Antigen presentation → B cells T helper cells B cells whose receptor matches a presented fragment multiply with the help of T helper cells and turn into cells that release antibodies. In animal models Borrelia disturb this maturation. Source 5↑ supplies B cells supply the antibodies. In germinal centres of the lymph nodes they mature with the help of T helper cells and then bind their target more tightly. In animal models Borrelia disturb the formation of these germinal centres. observed in studies Source 5
   ⚖ When the balance tips

   too much — If many B cells are activated, many antibodies form; in animal models the lymph nodes enlarge because B cells gather there.

   too little — If few B cells mature in germinal centres, fewer tightly binding antibodies form; in animal models Borrelia then remain longer in the tissue.

   observed in studies · Source 5

7. B cells → IgM antibodies Antibodies of the IgM class appear first. They consist of five linked units and can bind several bacteria at once. They also activate the complement system. Source 4↑ supplies With its many binding sites, IgM binds several bacteria at once and activates the complement system, a group of blood proteins that attacks the bacterial coat. established physiology Source 4
   ⚖ When the balance tips

   too much — If plenty of IgM has formed, more bacteria are bound and more complement is activated.

   too little — If little IgM has formed, for example at the very beginning before B cells have multiplied, few antibodies bind, and a test does not yet find any.

   established physiology · Source 4

8. IgM antibodies → IgG antibodies Class switch (AID) Later, B cells switch to the IgG class with the help of the enzyme AID. IgG antibodies bind their target more tightly and remain detectable in the blood for a long time. They mark the bacteria for phagocytes. Source 4, 5↑ supplies IgG marks the bacteria so that phagocytes engulf them and complement attacks their coat. Against a coat that keeps changing, however, this marking does not keep up everywhere in animal models. observed in studies Source 4, 6
   ⚖ When the balance tips

   too much — If plenty of IgG has formed, bacteria with matching coat proteins are cleared quickly; bacteria with an altered coat remain unaffected.

   too little — If little IgG has formed, for example in the first weeks after the bite, the bacteria are barely marked, and a test still finds little.

   observed in studies · Source 6, 4

9. IgG antibodies → Target structures bind to A short section of VlsE, called IR6, stays the same in every version. Antibodies against it, and against OspC or the flagellar protein p41, can be detected in the blood. Whatever version is present, IR6 remains a target. Source 7, 6↑ supplies Unchanging sections such as IR6 offer a target that all versions share. Antibodies against them can be detected in the blood, whatever version of VlsE is currently present. established physiology Source 7, 6
   ⚖ When the balance tips

   too much — If many antibodies against IR6, OspC or p41 have formed, more of them bind in the test, and the signal becomes stronger.

   too little — If few have formed, for example early after the bite, the signal stays weak; a test may then show nothing yet.

   established physiology · Source 7, 4

10. Antigenic variation → Target structures A short section of VlsE, called IR6, stays the same in every version. Antibodies against it, and against OspC or the flagellar protein p41, can be detected in the blood. Whatever version is present, IR6 remains a target. Source 7, 6↑ supplies Unchanging sections such as IR6 offer a target that all versions share. Antibodies against them can be detected in the blood, whatever version of VlsE is currently present. established physiology Source 7, 6
    ⚖ When the balance tips

    too much — If many antibodies against IR6, OspC or p41 have formed, more of them bind in the test, and the signal becomes stronger.

    too little — If few have formed, for example early after the bite, the signal stays weak; a test may then show nothing yet.

    established physiology · Source 7, 4

Further stations

• Borrelia in the tick — in the midgut, coat OspA Borrelia are spiral-shaped bacteria. In an unfed tick they sit in the midgut and carry mainly the protein OspA on their outer surface, which lets them attach there. OspA binds to a protein of the gut wall there. Source 1, 2↑ supplies OspA holds the bacteria in the tick's midgut by binding to a protein of the gut wall. In this way they outlast the time between two blood meals, which can be months. established physiology Source 2, 1
  ⚖ When the balance tips

  too much — If many bacteria sit in the tick gut, they multiply strongly at the next blood meal, and more of them can migrate to the salivary gland.

  too little — If few or no Borrelia sit in the tick gut, few or none reach the skin during feeding; not every tick carries them.

  observed in studies · Source 2, 1

• Innate immunity — TLR2 detects lipoproteins Phagocytes carry the receptor TLR2. It recognises the lipid-bearing proteins of the bacterial coat. The cell then releases signalling molecules and attracts further immune cells to the site. The phagocytes also engulf bacteria. Source 4↑ supplies TLR2 sets the defence in motion: the phagocyte releases messengers such as TNF and IL-6, vessels widen and further immune cells move in. At the same time phagocytes engulf and break down bacteria. established physiology Source 4
  ⚖ When the balance tips

  too much — If the response via TLR2 is strong, phagocytes release many messengers; more immune cells then gather in the tissue, and an inflammatory reaction develops.

  too little — If it is weak, for example under the influence of tick saliva proteins, immune cells notice the bacteria later, and the bacteria at first multiply undisturbed.

  observed in studies · Source 4, 2

• Antigenic variation — VlsE is rewritten On a circular piece of their genome, Borrelia continually swap sections of the coat protein VlsE for silent copies. Antibodies against an earlier version then no longer fit. In this way they evade the antibodies. Source 6↓ depletes Antigenic variation removes the bacteria from the reach of existing antibodies: each new version of VlsE looks foreign to them. In animal models Borrelia thus remain in the tissue for a long time despite antibodies. observed in studies Source 6
  ⚖ When the balance tips

  too much — If VlsE is rewritten often, many versions arise side by side, and the antibodies catch up with each new one only after a delay.

  too little — If the bacteria lack the circular piece with the silent copies, they cannot rewrite VlsE; in animal models such strains are cleared by the antibodies.

  observed in studies · Source 6

Cofactors in this pathway

• Zinc — Needed for signalling and proliferation of T and B cells; component of many zinc finger proteins Source 9In the ORY catalogue as a laboratory value: Zink
• Vitamin D — Calcitriol regulates genes in phagocytes, dendritic cells and lymphocytes via the vitamin D receptor Source 10In the ORY catalogue as a laboratory value: Vitamin D
• Iron — Needed for lymphocyte cell division and for the formation of oxygen radicals in phagocytes Source 12In the ORY catalogue as a laboratory value: Eisen
• Selenium — Component of selenoproteins such as the glutathione peroxidases in immune cells; they break down peroxides Source 11In the ORY catalogue as a laboratory value: Selen
• Manganese — Metal in enzymes and gene regulators of Borrelia; the bacteria manage without iron; so iron withholding spares them Source 8, 13

Sources

1. Radolf JD, Caimano MJ et al. Of ticks, mice and men: understanding the dual-host lifestyle of Lyme disease spirochaetes. Nat Rev Microbiol 2012 · PubMed 22230951
2. Kurokawa C, Lynn GE et al. Interactions between Borrelia burgdorferi and ticks. Nat Rev Microbiol 2020 · PubMed 32651470
3. Brissette CA, Gaultney RA. That's my story, and I'm sticking to it--an update on B. burgdorferi adhesins. Front Cell Infect Microbiol 2014 · PubMed 24772392
4. Petzke M, Schwartz I. Borrelia burgdorferi Pathogenesis and the Immune Response. Clin Lab Med 2015 · PubMed 26593255
5. Tracy KE, Baumgarth N. Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts. Front Immunol 2017 · PubMed 28265270
6. Norris SJ. vls Antigenic Variation Systems of Lyme Disease Borrelia: Eluding Host Immunity through both Random, Segmental Gene Conversion and Framework Heterogeneity. Microbiol Spectr 2014 · PubMed 26104445
7. Lawrenz MB, Hardham JM et al. Human antibody responses to VlsE antigenic variation protein of Borrelia burgdorferi. J Clin Microbiol 1999 · PubMed 10565921
8. Posey JE, Gherardini FC. Lack of a role for iron in the Lyme disease pathogen. Science 2000 · PubMed 10834845
9. Wessels I, Maywald M, Rink L. Zinc as a Gatekeeper of Immune Function. Nutrients 2017 · PubMed 29186856
10. Aranow C. Vitamin D and the immune system. J Investig Med 2011 · PubMed 21527855
11. Avery JC, Hoffmann PR. Selenium, Selenoproteins, and Immunity. Nutrients 2018 · PubMed 30200430
12. Nairz M, Weiss G. Iron in infection and immunity. Mol Aspects Med 2020 · PubMed 32461004
13. Troxell B, Yang XF. Metal-dependent gene regulation in the causative agent of Lyme disease. Front Cell Infect Microbiol 2013 · PubMed 24298449

Related pathways

• ASCA and ANCA — target structures
• Helicobacter pylori — igg antibodies
• IgE antibodies and mast cells — antigen presentation
• IgG antibodies to food — antigen presentation
• 8-OHdG — Zink, Eisen

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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