Does a Tick Bite Change the Immune Response to Lyme Disease?
A tick bite does more than deliver Borrelia
Tick feeding can alter the early immune environment
A 2026 mouse study found a different response with natural transmission
Does a tick bite change the immune response to Lyme disease? A 2026 laboratory study suggests that it can. Researchers found that Borrelia burgdorferi transmitted during the feeding of an infected blacklegged tick produced a different and more complex early immune response in mice than cultured bacteria injected under the skin.1
This is important because a tick is not simply a syringe that deposits Borrelia into the body. While feeding, the tick also introduces saliva and physically alters the skin at the bite site. Tick saliva contains biologically active substances that interact with immune defenses, while Borrelia burgdorferi has its own mechanisms for interacting with and evading the host immune response.1
Patients often ask me how Lyme disease affects the immune system and why the infection can produce such different responses from one person to another. This study does not answer those clinical questions directly, but it illustrates an important principle: how Borrelia enters a host may influence the immune response that follows.
For patients interested in the broader relationship between infection and immune regulation, I discuss this separately in my article on immune dysregulation in Lyme disease.
What Did the 2026 Study Examine?
Kundu and colleagues compared several ways mice could be exposed to Borrelia burgdorferi or to tick feeding.1
The researchers studied C3H/HeN mice exposed to infected Ixodes scapularis nymphs, uninfected ticks, or cultured multi-strain Borrelia burgdorferi injected subcutaneously. They then examined immune cells in the skin and spleen and measured circulating cytokines and chemokines.1
This design allowed the investigators to separate some of the effects of the bacteria from the effects associated with the tick itself.
The researchers reported that tick-transmitted Borrelia produced the strongest differences in recruited and resident immune-cell populations in both the skin and spleen. It also produced the greatest number of changes in circulating chemotactic mediators.1
How Was the Immune Response Different After a Tick Bite?
The immune response following infected-tick feeding was broader than the response observed after subcutaneous injection of cultured Borrelia.
Tick-transmitted Borrelia was associated with a mixture of type-1, type-2, and type-17 immune responses. Interestingly, some of these responses were also seen when uninfected ticks fed on the mice, suggesting that tick feeding itself contributed to the immune environment at the bite site.1
By comparison, subcutaneous inoculation with cultured Borrelia produced a more predominantly type-1 immune response.1
The details of these immune pathways are complicated, but the patient-facing point is simpler: the immune system was not responding only to Borrelia. It was responding to the combination of the bacteria, tick feeding, the skin injury, and components associated with the tick.
Why Does Tick Saliva Matter?
A feeding tick must remain attached long enough to obtain a blood meal. During that process, tick saliva interacts with the host’s local defenses.
The authors note that previous research has shown that tick saliva can modify several immune mechanisms relevant to Borrelia, including complement activity, chemotaxis, neutrophil responses, phagocytosis, and T-cell responses.1
These interactions may create a local environment that is more favorable for transmission and establishment of the spirochete.
That helps explain why experiments in which cultured Borrelia is injected through a needle do not necessarily reproduce every biological feature of infection acquired from an actual tick.
Did Tick-Transmitted Borrelia Behave Differently in the Skin?
There was also an interesting difference in detection of Borrelia at the skin site.
Borrelia DNA was detected in the skin of 50% of mice four days after infected-tick challenge and 100% by day six. In comparison, it was detected in none of the mice 24 hours after subcutaneous inoculation and in 17% at 72 hours.1
The authors considered this difference notable, although the finding needs to be interpreted within the limitations of early qPCR detection and the experimental model. The researchers did not detect Borrelia DNA in heart or joint tissues at these early time points, which they noted was expected because dissemination to those tissues takes longer in this model.1
These findings should not be translated into a timetable for infection in people. They instead reinforce the biological differences between natural tick transmission and experimental needle inoculation.
Could the Immune Response Help Borrelia Persist?
The researchers raise this possibility, but this part of the study requires particular caution.
They found that infected-tick feeding produced a dynamic combination of inflammatory and regulatory immune responses. The authors suggest that a broad but regulated response may help explain how Borrelia burgdorferi can persist in a reservoir host while maintaining the enzootic cycle.1
That is biologically interesting, but it does not demonstrate that the same mechanism explains persistent symptoms after Lyme disease treatment in people.
Why some patients continue to experience symptoms following treatment remains an important and unresolved clinical question. Multiple mechanisms have been proposed, and I discuss those separately in my overview of persistent Lyme disease mechanisms.
Does This Study Tell Us What Happens in People With Lyme Disease?
Not directly.
This was an experimental mouse study designed to examine early immune responses during tick feeding. It was not a study of patients with Lyme disease, and it did not examine symptoms, diagnostic testing, antibiotic treatment, treatment response, or long-term outcomes.1
Mouse models are useful for understanding biological mechanisms, but findings in mice cannot automatically be assumed to occur in people.
There is, however, human research showing that tick feeding can modify the immune environment of human skin. That provides additional evidence that the tick-host interaction itself deserves attention when researchers study naturally acquired tick-borne infections.2
Clinically, patients still need to be evaluated according to their exposure history, symptoms, physical findings, appropriate laboratory testing, and alternative diagnoses. Patients trying to understand the broader range of presentations can review my Lyme disease symptoms guide.
Why Does This Research Matter?
Many laboratory studies of Lyme disease necessarily simplify infection so that researchers can study one variable at a time. Cultured bacteria may be introduced through a needle, immune cells may be studied outside the body, or individual bacterial proteins may be examined separately.
Those experiments are valuable, but natural infection is more complicated.
During a real tick bite, Borrelia enters the skin while the tick is actively feeding. At the same time, tick saliva is interacting with local immune defenses, skin cells are being disrupted, immune cells are being recruited or altered, and the spirochete is adapting from the tick environment to the mammalian host.
The 2026 study is useful because it demonstrates experimentally that these differences are not merely theoretical: the immune response to tick-transmitted Borrelia was measurably different from the response to cultured bacteria introduced by needle.1
That does not change how Lyme disease should be diagnosed or treated today. It does remind us that naturally acquired Lyme disease involves a three-way interaction among the tick, Borrelia, and the host—and experimental models may capture only part of that biology.
Frequently Asked Questions
Does tick saliva affect the immune system?
Yes. Tick saliva contains biologically active substances that can interact with local immune defenses. Research has shown effects involving complement, immune-cell recruitment, phagocytosis, and other immune pathways. These effects may help ticks feed successfully and may also influence transmission of tick-borne pathogens.
Is getting Borrelia from a tick different from injecting the bacteria?
In experimental models, it can be. A 2026 mouse study found that tick-transmitted Borrelia burgdorferi produced a broader immune response than cultured bacteria injected under the skin. Natural tick transmission also introduces tick saliva and occurs while the tick is actively feeding.
Does this study prove why Lyme disease symptoms persist?
No. The study examined early immune responses in mice. Although the researchers discussed how a regulated immune response might contribute to persistence of Borrelia in reservoir hosts, the study did not investigate persistent symptoms or treatment outcomes in people.
Does this research change Lyme disease treatment?
No. This was a mechanistic study rather than a treatment trial. It helps researchers understand what happens during natural tick transmission but does not establish a different antibiotic regimen or duration of treatment.
Does everyone have the same immune response to a Lyme infection?
No. Immune responses can vary among individuals and may be influenced by many factors. This particular study does not explain why individual patients develop different symptoms or outcomes because it was conducted in an experimental mouse model.
Clinical Takeaway
Patients sometimes think of a tick as simply delivering Borrelia burgdorferi through the skin. The biology is considerably more complicated. A feeding tick introduces saliva, interacts with local immune defenses, disrupts the skin barrier, and delivers Borrelia into an immune environment that is changing during the blood meal.
The 2026 study provides experimental evidence that tick-transmitted Borrelia can produce a different early immune response from cultured bacteria introduced by needle. However, because the study was performed in mice, it should not be used to explain an individual patient’s symptoms, predict treatment response, or establish why symptoms sometimes persist after treatment.
For patients, the useful message is that Lyme disease begins as an interaction among the tick, the bacteria, and the host—not simply exposure to Borrelia alone.
Related Articles
For additional information about Lyme disease, immune function, and clinical presentation:
Disseminated Lyme Disease More Likely in Those With Weakened Immune System
First Symptoms of Lyme Disease: Why the Rash Is Often Missing
Lyme Disease and Autoimmunity: Why Symptoms May Persist
References
- Kundu S, Joyner G, Gomes-Solecki M. Innate immune responses to Borrelia burgdorferi during tick-feeding: mechanistic insights relevant to Lyme disease. mBio. 2026;17(5):e03971-25.
- Strobl J, Mündler V, Müller S, et al. Tick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission. J Clin Invest. 2022;132(21):e161188.
Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.
Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention
