Mucosal innate response stimulation induced by lipopolysaccharide protects against Bordetella pertussis colonization.

Non-specific enhancement of the airways innate response has been shown to impair lung infections in several models of infection such diverse as influenza A, Streptococcus pneumoniae, and Aspergillus niger. Our aim was to evaluate whether a similar event could operate in the context of Bordetella pertussis respiratory infection, not only to enrich the knowledge of host-bacteria interaction but also to establish immunological basis for the development of new control strategies against the pathogen. Using a B. pertussis intranasal infection model and coadministration of different TLR agonists at the moment of the infection, we observed that the enhancement of innate response activation, in a TLR4-dependent way, could efficiently impair B. pertussis colonization (P < 0.001). While LPS from different microbial sources were equally effective in promoting this effect, flagellin and poly I:C coadministration, in spite of inducing expression of innate response markers TNFalpha, CXCL2, CXCL10 and IL6, was not effective to prevent B. pertussis colonization. Our results indicate that during the early stage of infection, specific anti-microbial mechanisms triggered by TLR4 stimulation are able to impair B. pertussis colonization. These findings could complement our current view of the role of TLR4-dependent processes that contribute to anti-pertussis immunity.

Differences of circulating Bordetella pertussis population in Argentina from the strain used in vaccine production.

In Argentina, as in other countries, the number of pertussis cases has been increasing, even in highly vaccinated zones. Many reports suggest that the decline of vaccine efficacy due to antigenic shifts in the circulating Bordetella pertussis might be among the factors that contribute to pertussis re-emergence in different parts of the world. To evaluate the incidence of this factor in Argentina, we decided to characterize the circulating bacteria of an important demographic area of this country in comparison with the strain used for vaccine production. From 1997 to 2003 we collected nasopharyngeal samples from pediatric patients with signs of Bordetella infection hospitalized in the metropolitan area of Buenos Aires and La Plata, Argentina. From these samples we identified 28 B. pertussis, which were characterized by biochemical techniques, PCR, DNA fingerprint, prn and ptx genes sequencing, and lipopolysaccharides (LPS) pattern. BOX-PCR from B. pertussis isolates yielded one cluster containing 13 isolates and some smaller ones, being all fingerprints different from the vaccine strain. Differences between Argentinean circulating bacteria and the vaccine strain were also observed for the Prn and Ptx variants as well as for the LPS pattern. Moreover, this last pattern seemed to change over the years. In addition, we identified two B. bronchiseptica. The presence of this Bordetella species together with the observed differences between circulating B. pertussis and the strain used in vaccine production should be considered for the development of an improved vaccine.