PNAS: revealing the mechanism by which Ixodes tick salivary adenotoxin promotes Lyme disease transmission

Ticks are arthropods that specialize in sucking blood and, because they require multiple host changes during the development cycle, are also the most widespread arthropod vectors
other than mosquitoes that transmit human and animal pathogens.
More than 28 species of ticks are known to cause a variety of human diseases, such as Lyme disease and spotted fever ricketts' disease, which can even lead to death
due to misdiagnosis and delayed treatment.
Lyme disease is the leading arbo-borne infectious disease in the northern hemisphere, with nearly 480,000 Lyme cases in the United States and nearly 230,000 in Western Europe each year, mainly transmitted by ticks, and its pathogen is Borrelia burgdorferi
.
Lyme disease is more common in forestry workers and outdoor workers, and is more common
in northeast China.
After human infection with Treponema Lyme disease through tick bites, the incubation period in the body is generally about 7 days, and the typical symptoms after the onset are erythema migrans, and the middle stage is often accompanied by severe malaise, headache, arthritis and myocarditis
.
The number of cases of Lyme disease is increasing year by year, but no vaccine has been approved for marketing
at present.

The team of Lai Cheng, a researcher at the Kunming Institute of Zoology, Chinese Academy of Sciences, focuses on toxic animals and animal toxins, is committed to the material basis and molecular mechanism of animal survival strategies and environmental adaptation, and has made a series of explorations in the pathogen-host interaction mechanism mediated by the bioavailability of toxins by toxic pathogens, such as the mechanism of pathogen transmission assisted by Aedes aegypti salivary adenotoxin (Nature Immunology.
2018; 19:342-353), bat salivary adenotoxin promotes viral transmission (PNAS.
2022; 119: e2110647119) and others
.
This time, the research team, together with the team of Cao Wuchun, a researcher at the Beijing Institute of Microbiology and Epidemiology, and Shahid Karim, a professor at the University of Southern Mississippi, found that there was a 15 kDa toxin targeting lymphotoxin receptor (LTβR) IpSAP (I.
persulcatus salivary protein）
。 IpSAP promotes Borrelia gasseri (B) by inhibiting LTβR receptors and downstream signal transduction, forming early local immunosuppression at the site of Lyme disease infection in mice (B.
Garinii).

Further studies have found that the combination of IpSAP recombinant protein and MnJ adjuvant immunized mice can effectively reduce the efficiency of transmission of Treponema Lyme disease by the bite of Ixodes parochrode, and has a significant protective effect
against the transmission of Treponema leigh simulated by salivary gland extracts of Ixodes ovale ticks and Ixodes ovale.
This study deepens the understanding of the molecular mechanism of tick-borne Lyme disease, clarifies that LTβR is a key molecule in host resistance to Treponema Lyme infection, and expands the idea
of developing a broad-spectrum Lyme disease vaccine that blocks vector transmission routes from the perspective of tick salivary immunosuppressive toxins.

The research results were recently published in PNAS under the title Interference with LTβR signaling by tick saliva facilitating transmission of Lyme disease spirochetes
.
The research work has been supported
by the National Natural Science Foundation of China, the Chinese Academy of Sciences, the Department of Science and Technology of Yunnan Province, and Shanxi Agricultural University.

Kunming Institute of Animals et al.
revealed the mechanism of Ixodes tick salivary gland toxin promoting Lyme disease transmission