Intragastric and Intranasal Administration of Lactobacillus paracasei NCC2461 Modulates Allergic Airway Inflammation in Mice

Abstract

Introduction. Preclinical and clinical evidences for a role of oral probiotics in the management of allergic diseases are emerging. Aim. We aimed at testing the immunomodulatory effects of intranasal versus intragastric administration of Lactobacillus paracasei NCC2461 in a mouse model of allergic airway inflammation and the specificity of different probiotics by comparing L. paracasei NCC2461 to Lactobacillus plantarum NCC1107. Methods. L. paracasei NCC2461 or L. plantarum NCC1107 strains were administered either intragastrically (NCC2461) or intranasally (NCC2461 or NCC1107) to OVA-sensitized mice challenged with OVA aerosols. Inflammatory cell recruitment into BALF, eotaxin and IL-5 production in the lungs were measured. Results. Intranasal L. paracasei NCC2461 efficiently protected sensitized mice upon exposure to OVA aerosols in a dose-dependent manner as compared to control mice. Inflammatory cell number, eotaxin and IL-5 were significantly reduced in BALF. Intranasal supplementation of L. paracasei NCC2461 was more potent than intragastric application in limiting the allergic response and possibly linked to an increase in T regulatory cells in the lungs. Finally, intranasal L. plantarum NCC1107 reduced total and eosinophilic lung inflammation, but increased neutrophilia and macrophages infiltration. Conclusion. A concerted selection of intervention schedule, doses, and administration routes (intranasal versus intragastric) may markedly contribute to modulate airway inflammation in a probiotic strain-specific manner.

Figure 1

Protocols of probiotic strains administration and subsequent effect of intragastric L. paracasei NCC2461 on total cell number in BALF of OVA-challenged mice. Mice were sensitized intraperitoneally (i.p.) twice with OVA and subsequently challenged with OVA aerosol 3 times. Mice received NCC2461 intragastrically (i.g.) 12 times before, after, and in between the 2 i.p. sensitizations (a) or 4 times before, after and in between each OVA challenge (b). Total cell count in the BALF (n = 10) mice per group. In this representative experiment, data are expressed as mean ± SD; *P < 0.05 (c).

Figure 2

Effect of intragastric versus intranasal L. paracasei NCC2461 administration on lung airway inflammation. L. paracasei NCC2461 (1 × 10⁹ CFU) or PBS were either administered intragastrically (i.g.) or intranasally (i.n.) in OVA-challenged mice. Total cell counts (a) and differential cell counts (b) in the BALF. Eotaxin (c) and IL-5 levels (d) in lung homogenate were quantified by ELISA. Histograms are mean ± SD obtained from one representative experiment, n = 10 mice per group; *P < 0.05, **P < 0.005, ***P < 0.0005.

Figure 3

Effect of intranasal L. paracasei NCC2461 and L. plantarum NCC1107 on lung airway inflammation. L. paracasei NCC2461 (1 × 10⁹ CFU), L. plantarum NCC1107 (1 × 10⁹ CFU), or PBS were administered intranasally (i.n.) in OVA-challenged mice. Total (a) and differential (b) cell counts were performed in the BALF. Eotaxin (c) and IL-5 levels (d) in lung homogenate were quantified by ELISA. Lung sections were PAS stained (results are expressed as % of PAS positive cells (e)) and H&E stained (f), reflecting the severity and localization of inflammation (magnification ×10). In this representative experiment, histograms are mean ± SD from 10 animals; *P < 0.05, **P < 0.005, ***P < 0.0005.

Figure 4

Percentage of FoxP3 positive cells in the CD4⁺CD25⁺ T cell population in the lung of mice treated intranasally with PBS or with NCC2461. One representative experiment out of two independent experiments. **P < 0.005.