Postimmunobiotics increase resistance to primary respiratory syncytial virus infection and 2 secondary pneumococcal pneumonia

RAYA TONETTI, FERNANDA; TOMOKIYO, MIKADO; FUKUYAMA, KOHTARO; ELEAN, MARIANO; ORTIZ MOYANO, RAMIRO; YAMAMURO, HIKARI; QUILODRAN-VEGA, SANDRA; KURATA, SHOICHIRO; VILLENA, JULIO; KITAZAWA, HARUKI

Beneficial Microbes

Wageningen Academic

Lugar: 6700 AE Wageningen; Año: 2022

Previously, we demonstrated that postimmunobiotics derived from Lactobacillus gasseri TMT36, 17 TMT39, and TMT40 strains (HK36, HK39 and HK40, respectively) differentially regulated Toll- 18 like receptor 3 (TLR3)-mediated antiviral respiratory immunity in infant mice. In this work, we 19 investigated whether the HK36, HK39 and HK40 nasal treatments were able to improve the 20 resistance against primary respiratory syncytial virus (RSV) infection and secondary 21 pneumococcal pneumonia. Our results demonstrated that the three treatments increased the 22 resistance to primary viral infection by reducing variations in body weight, RSV titers and lung 23 damage of infected infant mice. Postimmunobiotics significantly enhanced the expressions of 24 IFN-λ, IFN-β, IFN-γ, IL-1β, IL-6, IL-27, Mx1, RNAseL and OAS1 genes and decreased TNF-α in 25 alveolar macrophages of RSV-challenged mice. In addition, the studies in the model of RSV- 26 Streptococcus pneumoniae superinfection showed that the HK39 and HK40 treatments were 27 capable of reducing lung damage, lung bacterial cell counts, and the dissemination of S. 28 pneumoniae into the blood of infant mice. The protective effect was associated with increases in 29 IFN-β, IFN-γ, IL-10, and IL-27 in the respiratory tract. This study demonstrates that the nasal 30 application of the postimmunobiotics HK39 and HK40 stimulates innate respiratory immunity 31 and enhances the defenses against primary RSV infection and secondary pneumococcal 32 pneumonia offering an alternative to combat respiratory superinfections in children, which can be 33 fatal.