A deep rough type structure in Bordetella bronchiseptica lipopolysaccharide affects the host immune response.

SISTI, FEDERICO; FERNANDEZ, JULIETA; HIGGINS, SARAH; MILLS, KINGSTON; HOZBOR, DANIELA FLAVIA

Baltimore Maryland

Simposio; 9no Simposio de Bordetella; 2010

It is well known that Bordetella bronchiseptica lipopolysaccharide plays an essential role in bacteria-host interaction. Using a defective mutant lacking O antigen with a deep rough structure (named BbLP39), we have demonstrated the importance of the complete LPS structure for effective colonization of mice with  B. bronchiseptica. Moreover, we observed that this mutant had diminished  ability to adhere to host cells. Here we showed that the deep rough mutant BbLP39 was able to infect and persist in the lungs of TLR4-defective mice beyond 5 days post infection. However, unlike the parental strain, which resulted in deaths in 100% of infected mice, infection with BbLP39 was not lethal, over a range of dose used for the intranasal  challenge.. However, the infection persisted in TLR4-defective mice following infection with a range of doses of BbLP39. To test if our findings reflect difference in the immune responses to the deep rough mutant compared with the parental strain, we examined cytokine production in vivo and in vitro using different forms of purified LPS. Despite the fact that the deep rough LPS has the same lipid A structure of the parental LPS, the BbLP39 LPS induced significantly higher TNF-a and IL-10 mRNA expression (3 and 7 times respectively) when compared with controls. Experiments  with bone marrow dendritic cells showed that deep rough LPS is a potent activator of IL-10 production. Our findings demonstrate for the first time differences in host response due to distal LPS structures, supporting the hypothesis that differences in LPS structure observed between strains may be influence the interaction between B. bronchiseptica and its hosts.