Treating insect-bite hypersensitivity in horses with active vaccination against IL-5

Fettelschoss‐Gabriel, Antonia; Fettelschoss, Victoria; Thoms, Franziska; Giese, Christoph; Daniel, M.J.; Olomski, Florian; Kamarachev, Jivko; Birkmann, Katharina; Bühler, Maya; Kummer, M; Zeltiņš, Andris; Marti, Eliane; Kündig, Thomas M.; Bachmann, Martin F.

doi:10.1016/j.jaci.2018.01.041

Cited by 64 publications

(112 citation statements)

References 49 publications

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“…In addition, we observed increased T‐cell numbers in the bronchoalveolar lavage fluid but not in the lung tissue of bite‐sensitized mice challenged with the mosquito SGE . Many other works have shown the presence of eosinophils in the arthropod bite site of different host species . Of note, the proportion of eosinophils and neutrophils in the skin following bite may vary depending on the haematophagous arthropod studied, on the vertebrate host species and on their immune status (naïve versus immune/sensitized), a finding also observed in our study.…”

Section: Discussionsupporting

confidence: 82%

“…37 Many other works have shown the presence of eosinophils in the arthropod bite site of different host species. [75][76][77][78][79] Of note, the proportion of eosinophils and neutrophils in the skin following bite may vary depending on the haematophagous arthropod studied, on the vertebrate host species and on their immune status (na€ ıve versus immune/sensitized), a finding also observed in our study.…”

Section: Discussionsupporting

confidence: 68%

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Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non‐sensitized mice reveals saliva‐dependent and immune‐dependent phenotypes

et al. 2019

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Summary During probing and blood feeding, haematophagous mosquitoes inoculate a mixture of salivary molecules into their vertebrate hosts’ skin. In addition to the anti‐haemostatic and immunomodulatory activities, mosquito saliva also triggers acute inflammatory reactions, especially in sensitized hosts. Here, we characterize the oedema and the cellular infiltrate following Aedes aegypti mosquito bites in the skin of sensitized and non‐sensitized BALB/c mice by flow cytometry. Ae. aegypti bites induced an increased oedema in the ears of both non‐sensitized and salivary gland extract‐ (SGE‐)sensitized mice, peaking at 6 hr and 24 hr after exposure, respectively. The quantification of the total cell number in the ears revealed that the cellular recruitment was more robust in SGE‐sensitized mice than in non‐sensitized mice, and the histological evaluation confirmed these findings. The immunophenotyping performed by flow cytometry revealed that mosquito bites were able to produce complex changes in cell populations present in the ears of non‐sensitized and SGE‐sensitized mice. When compared with steady‐state ears, the leucocyte populations significantly recruited to the skin after mosquito bites in non‐sensitized and sensitized mice were eosinophils, neutrophils, monocytes, inflammatory monocytes, mast cells, B‐cells and CD4+ T‐cells, each one with its specific kinetics. The changes in the absolute number of cells suggested two cell recruitment profiles: (i) a saliva‐dependent migration; and (ii) a migration dependent on the immune status of the host. These findings suggest that mosquito bites influence the skin microenvironment by inducing differential cell migration, which is dependent on the degree of host sensitization to salivary molecules.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 68%

Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non‐sensitized mice reveals saliva‐dependent and immune‐dependent phenotypes

et al. 2019

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“…To our knowledge, this approach has not been previously reported in ruminants. One recent study reported the effectiveness of IL‐5 vaccination in reducing eosinophilia and insect‐bite hypersensitivity in horses . As only small amounts of reasonably easy‐to‐prepare reagents were needed, this approach was considered more cost‐effective and feasible for large animal experimentation, such as sheep.…”

Section: Discussionmentioning

confidence: 99%

Increased susceptibility to Haemonchus contortus infection by interleukin‐5 modulation of eosinophil responses in sheep

Hernández

Meeusen

Rodrı́guez

et al. 2019

Parasite Immunology

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Eosinophils are prominent effector cells in immune responses against gastrointestinal nematode infections in ruminants, but their in vivo role has been hard to establish in large animals. Interleukin‐5 is a key cytokine in the induction and stimulation of anti‐parasitic eosinophil responses. This study attempted to modulate the eosinophil response in sheep through vaccination with recombinant interleukin‐5 (rIL‐5) and determine the effect on subsequent Haemonchus contortus infection. Nematode‐resistant Canaria Hair Breed (CHB) sheep vaccinated with rIL‐5 in Quil‐A adjuvant, had lower blood eosinophil counts and higher mean worm burdens than control sheep vaccinated with Quil‐A adjuvant alone. In addition, adult worms in IL‐5‐vaccinated sheep were significantly longer with higher eggs in utero in female worms, supporting an active role of eosinophils against adult parasites in CHB sheep. These results confirm that eosinophils can play a direct role in effective control of H contortus infection in sheep and offer a new approach to study immune responses in ruminants.

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“…Addition of the atopic cytokine milieu alone already induced a significant TSLP upregulation, and when combined with Pam3CSK4 or Poly (I:C), it synergistically further upregulated TSLP expression. In skin allergic conditions including IBH, clinical signs are exacerbated by secondary bacterial infections . As mentioned, Pam3CSK4 is a constituent of bacterial membranes recognized by TLR1/2 heterodimers .…”

Section: Discussionmentioning

confidence: 99%

Toll‐like receptor‐ligand induced thymic stromal lymphopoietin expression in primary equine keratinocytes

Cvitaš

Galichet

Ling

et al. 2019

Veterinary Dermatology

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Background Thymic stromal lymphopoietin (TSLP) plays a key role in the development of allergic inflammation. Little is known about possible triggers of equine TSLP expression. Hypothesis/objectives To investigate TSLP expression in equine insect bite hypersensitivity (IBH) skin lesions. The capacity of TLR 1‐8 ligands (L) and of atopic cytokine milieu as potential triggers of TSLP and of interleukin (IL)‐6 as a downstream effector molecule of TLR signalling, were examined in primary equine keratinocyte cultures. Animals Lesional skin from IBH‐affected and healthy skin from control‐horses (n = 9 each group) was sampled. Methods and materials Keratinocyte cultures were established from six healthy horses and stimulated with TLR 1‐8‐L, and with IL‐4 and tumor necrosis factor‐α, to mimic an atopic inflammation cytokine milieu. TSLP and IL‐6 gene expression was assessed by quantitative real‐time PCR. Results Expression of TSLP was significantly greater in IBH lesions compared to healthy skin. TLR 1‐8‐L significantly upregulated TSLP expression in keratinocytes. The strongest upregulation was induced by TLR 1/2‐L and TLR 3‐L. Combination of atopic cytokine milieu and TLR 1/2‐L or TLR 3‐L further increased TSLP expression. TLR‐L 1‐5 stimulation significantly upregulated IL‐6 expression. Conclusions and clinical importance The data herein suggest that the upregulation of TSLP expression in lesional skin of IBH‐affected horses might play a role in IBH development. Moreover, TSLP expression is induced by TLR‐L, in particular by TLR 1/2‐L and TLR 3‐L, and is further increased by atopic cytokine milieu, indicating a mechanism for TSLP‐mediated exacerbation of IBH.

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Treating insect-bite hypersensitivity in horses with active vaccination against IL-5

Abstract: Our therapeutic vaccine inducing autoantibodies against self IL-5 brings biologics to horses, is the first successful immunotherapeutic approach targeting a chronic disease in horses, and might facilitate development of a similar vaccine against IL-5 in human subjects.

Cited by 64 publications

References 49 publications

Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non‐sensitized mice reveals saliva‐dependent and immune‐dependent phenotypes

Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non‐sensitized mice reveals saliva‐dependent and immune‐dependent phenotypes

Increased susceptibility to Haemonchus contortus infection by interleukin‐5 modulation of eosinophil responses in sheep

Toll‐like receptor‐ligand induced thymic stromal lymphopoietin expression in primary equine keratinocytes

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