Commensal respiratory bacteria Dolosigranulum pigrum 040417 beneficially modulates immune response mediated by activation of TLR3

PAULRAJ KANMANI; MARIA FERNANDA RAYA TONETTI; RAMIRO ORTIZ MOYANO; MARIA GUADALUPE VIZOSO PINTO; SUSANA ALVAREZ; HO JUN KIM; HARUKI KITAZAWA; JULIO VILLENA

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica, LXVI Reunión Anual de la Sociedad Argentina de Inmunología, Reunión Anual de la Sociedad Argentina de Fisiología; 2018

SAI-SAIC

The human commensal respiratory bacterium Dolosigranulum pigrum 040417 (DP) increases the resistance of infant mice to Respiratory Syncytial Virus infection. The immunological mechanisms involved in the beneficial effect of DP were not investigated before. In this work, the effect of DP on the innate antiviral respiratory immune response triggered by TLR3 activation was investigated. Infant BALB/c mice (3-week-old) were nasally treated with 108 DP cells for two consecutive days. On the third day, treated mice were nasally challenged with poly(I:C) (250 μg/mouse) for three consecutive days. Untreated control mice were challenged with poly(I:C) similarly. Lung damage and the respiratory and systemic immune response were studied two days after the last poly(I:C) administration. TLR3 activation induced a marked lung damage that was accompanied by pro-inflammatory factors production and inflammatory cells recruitment into the respiratory tract. However, lung tissue injury was significantly lower in DP-treated mice. Lower levels of albumin concentrations and LDH activity (control=101.9±4.1, DP=67.3±2.5 UI/ml) were found in the bronchoalveolar lavage (BAL) of DP-treated mice compared to controls, indicating a lower alteration of the alveolar-capillary barrier and reduced cellular damage. Poly(I:C) increased neutrophils and macrophages numbers in the lung, and TNF-α and IL-6 in serum and BAL in both experimental groups. However, the DP group had significantly higher levels of TNF-α (control=115.6±3.2, DP=163.1±2.9 pg/ml) and IL-6. DP also increased lung CD3+CD4+IL-10+ T cells and CD11c+SiglecF+IFN-β+ alveolar macrophages, with the consequent increases in respiratory levels of IL-10 (control=379.1±12.1, DP=451.4±11.5 pg/ml) and IFN-β (control=121.7±3.1, DP=152.9±3.4 pg/ml). No differences were observed between the groups when evaluating CD3+CD4+IFN-γ+ T cells or IFN-γ levels. These results suggest that nasal DP administration differentially modulate the respiratory immune response triggered by TLR3 activation, improving antiviral immunity and reducing inflammatory damage.