Co-exposure to lipopolysaccharide and desert dust causes exacerbation of ovalbumin-induced allergic lung inflammation in mice via TLR4/MyD88-dependent and -independent pathways

Yahao Ren; Takamichi Ichinose; Miao He; Seiichi Youshida; Masataka Nishikawa; Guifan Sun

doi:10.1186/s13223-019-0396-4

Co-exposure to lipopolysaccharide and desert dust causes exacerbation of ovalbumin-induced allergic lung inflammation in mice via TLR4/MyD88-dependent and -independent pathways

Allergy Asthma Clin Immunol. 2019 Dec 18:15:82. doi: 10.1186/s13223-019-0396-4. eCollection 2019.

Authors

Yahao Ren¹, Takamichi Ichinose², Miao He³, Seiichi Youshida², Masataka Nishikawa⁴, Guifan Sun³

Affiliations

¹ 1Department of Nutritional and Food Hygiene, School of Public Health, China Medical University, Shenyang, 110122 China.
² 2Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita, 870-1201 Japan.
³ 3Department of Environmental Health, School of Public Health, China Medical University, Shenyang, 110122 China.
⁴ 4Environmental Chemistry Division, National Institute for Environmental Studies, Ibaraki, 305-8506 Japan.

Abstract

Background: Lipopolysaccharide (LPS) often presents in high concentrations in particulate matter (PM), few studies have reported the enhancing effects of both LPS and PM on airway inflammation in mice and the role of toll-like receptors (TLRs) in this process. Asian sand dust (ASD) is observed most frequently during the spring. This study aimed to clarify the role of TLRs in murine lung eosinophilia exacerbated by ASD and LPS.

Methods: The effects of LPS and ASD co-treatment on ovalbumin (OVA)-induced lung eosinophilia were investigated using wild-type (WT), TLR2^-/-, TLR4^-/-, and adaptor protein myeloid differentiation factor 88 (MyD88)^-/- BALB/c mice. ASD was heated (H-ASD) to remove the toxic organic substances. WT, TLR2^-/-, TLR4^-/- and MyD88^-/- BALB/c mice were intratracheally instilled with four different combinations of LPS, H-ASD and OVA treatment. Subsequently, the pathological changes in lungs, immune cell profiles in bronchoalveolar lavage fluid (BALF), inflammatory cytokines/chemokines levels in BALF and OVA-specific immunoglobulin (Ig) in serum were analyzed.

Results: In WT mice, H-ASD + LPS exacerbated OVA-induced lung eosinophilia. This combination of treatments increased the proportion of eosinophils and the levels of IL-5, IL-13, eotaxin in BALF, as well as the production of OVA-specific IgE and IgG1 in serum compared to OVA treatment alone. Although these effects were stronger in TLR2^-/- mice than in TLR4^-/- mice, the expression levels of IL-5, IL-13, eotaxin were somewhat increased in TLR4^-/- mice treated with OVA + H-ASD + LPS. In MyD88^-/- mice, this pro-inflammatory mediator-induced airway inflammation was considerably weak and the pathological changes in lungs were negligible.

Conclusions: These results suggest that LPS and H-ASD activate OVA-induced Th2 response in mice, and exacerbate lung eosinophilia via TLR4/MyD88, TLR4/TRIF and other TLR4-independent pathways.

Keywords: Airway-inflammation; Lipopolysaccharide; MyD88; TLR4; TRIF.