Ascaris larval infection and lung invasion directly induce severe allergic airway disease in mice

Jill E. Weatherhead, Paul Porter, Amy Coffey, Dana Haydel, Leroy Versteeg, Bin Zhan, Ana Clara Gazzinelli Guimarães, Ricardo Fujiwara, Ana M. Jaramillo, Maria Elena Bottazzi, Peter J. Hotez, David B. Corry, Coreen M. Beaumiera

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Ascaris lumbricoides (roundworm) is the most common helminth infection globally and a cause of lifelong morbidity that may include allergic airway disease, an asthma phenotype. We hypothesize that Ascaris larval migration through the lungs leads to persistent airway hyperresponsiveness (AHR) and type 2 inflammatory lung pathology despite resolution of infection that resembles allergic airway disease. Mice were infected with Ascaris by oral gavage. Lung AHR was measured by plethysmography and histopathology with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) stains, and cytokine concentrations were measured by using Luminex Magpix. Ascaris-infected mice were compared to controls or mice with allergic airway disease induced by ovalbumin (OVA) sensitization and challenge (OVA/ OVA). Ascaris-infected mice developed profound AHR starting at day 8 postinfection (p.i.), peaking at day 12 p.i. and persisting through day 21 p.i., despite resolution of infection, which was significantly increased compared to controls and OVA/OVA mice. Ascaris-infected mice had a robust type 2 cytokine response in both the bronchoalveolar lavage (BAL) fluid and lung tissue, similar to that of the OVA/OVA mice, including interleukin-4 (IL-4) (P<0.01 and P < 0.01, respectively), IL-5 (P<0.001 and P<0.001), and IL-13 (P< 0.001 and P<0.01), compared to controls. By histopathology, Ascaris-infected mice demonstrated early airway remodeling similar to, but more profound than, that in OVA/OVA mice. We found that Ascaris larval migration causes significant pulmonary damage, including AHR and type 2 inflammatory lung pathology that resembles an extreme form of allergic airway disease. Our findings indicate that ascariasis may be an important cause of allergic airway disease in regions of endemicity.

Original languageEnglish (US)
Article numbere00533
JournalInfection and immunity
Volume86
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Ascaris
Ovalbumin
Lung
Infection
Pathology
Ascariasis
Cytokines
Ascaris lumbricoides
Airway Remodeling
Periodic Acid
Plethysmography
Interleukin-13
Helminths
Interleukin-5
Bronchoalveolar Lavage Fluid
Hematoxylin
Eosine Yellowish-(YS)
Interleukin-4
Coloring Agents
Asthma

Keywords

  • Airway hyperreactivity
  • Allergic airway disease
  • Ascaris
  • Asthma
  • Hygiene hypothesis

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Weatherhead, J. E., Porter, P., Coffey, A., Haydel, D., Versteeg, L., Zhan, B., ... Beaumiera, C. M. (2018). Ascaris larval infection and lung invasion directly induce severe allergic airway disease in mice. Infection and immunity, 86(12), [e00533]. https://doi.org/10.1128/IAI.00533-18

Ascaris larval infection and lung invasion directly induce severe allergic airway disease in mice. / Weatherhead, Jill E.; Porter, Paul; Coffey, Amy; Haydel, Dana; Versteeg, Leroy; Zhan, Bin; Guimarães, Ana Clara Gazzinelli; Fujiwara, Ricardo; Jaramillo, Ana M.; Bottazzi, Maria Elena; Hotez, Peter J.; Corry, David B.; Beaumiera, Coreen M.

In: Infection and immunity, Vol. 86, No. 12, e00533, 01.12.2018.

Research output: Contribution to journalArticle

Weatherhead, JE, Porter, P, Coffey, A, Haydel, D, Versteeg, L, Zhan, B, Guimarães, ACG, Fujiwara, R, Jaramillo, AM, Bottazzi, ME, Hotez, PJ, Corry, DB & Beaumiera, CM 2018, 'Ascaris larval infection and lung invasion directly induce severe allergic airway disease in mice', Infection and immunity, vol. 86, no. 12, e00533. https://doi.org/10.1128/IAI.00533-18
Weatherhead, Jill E. ; Porter, Paul ; Coffey, Amy ; Haydel, Dana ; Versteeg, Leroy ; Zhan, Bin ; Guimarães, Ana Clara Gazzinelli ; Fujiwara, Ricardo ; Jaramillo, Ana M. ; Bottazzi, Maria Elena ; Hotez, Peter J. ; Corry, David B. ; Beaumiera, Coreen M. / Ascaris larval infection and lung invasion directly induce severe allergic airway disease in mice. In: Infection and immunity. 2018 ; Vol. 86, No. 12.
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