Epicutaneously applied D er p 2 induces a strong T H 2‐biased antibody response in C 57 BL /6 mice, independent of functional TLR 4

• Published in: Allergy (Copenhagen) Vol. 69; no. 6; pp. 741 - 751
• Main Authors: Stremnitzer, C., Manzano‐Szalai, K., Starkl, P., Willensdorfer, A., Schrom, S., Singer, J., Reichart, U., Akira, S., Jensen‐Jarolim, E.
• Format: Journal Article
• Language: English
• Published: 01-06-2014
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.12399

Abstract
Background
The major house dust mite allergen
D
er p 2 is a structural and functional homologue of
MD
‐2 within the
TLR
4–
CD
14–
MD‐
2 complex. An asthma mouse model in
TLR
4‐deficient mice recently suggested that the allergic immune response against
D
er p 2 is solely dependent on
TLR
4 signaling. We investigated whether similar mechanisms are important for
D
er p 2 sensitization via the skin.
Methods
In an epicutaneous sensitization model, the response to recombinant
D
er p 2 in combination with or without lipopolysaccharide (
LPS
) was compared between
C
57
BL
/6
WT
and
TLR
4‐deficient mice. We further analyzed possible adjuvant function of exogenous cysteine proteases.
Results
Sensitization with r
D
er p 2 induced similar levels of allergen‐specific
I
g
G
1 and
I
g
E
antibodies in both mouse strains.
LPS
increased the systemic (antibody levels, cytokine release by restimulated splenocytes) and local (infiltration of immune cells into the skin) Th2 immune responses, which against our expectations were stronger in the absence of functional
TLR
4 expression. Barrier disruption by papain, a protease with structural homology to
D
er p 1, did not enhance the sensitization capacity of
rD
er p 2. However, the presence of
LPS
increased the stability of r
D
er p 2 against the protease.
Conclusion
Our data suggest that r
D
er p 2 alone can cause a strong
T
H
2‐biased response via the skin being enhanced in the presence of
LPS
. This response is not reliant on functional
TLR
4, but
vice versa

TLR
4 expression rather protects against epicutaneous sensitization to house dust mite allergen
D
er p 2.