Both wild-type and sigE-deficient RB50 colonized the nasal cavity

Both wild-type and sigE-deficient RB50 colonized the nasal cavity at comparable levels, peaking on day 3 post-inoculation, and stabilizing at about 104-5 CFU by 2 weeks post-inoculation (Figure 3). Both strains also showed similar colonization kinetics in the lower respiratory tract of C57BL/6 mice, peaking in numbers on days 3 and 7 post-inoculation in the trachea and lungs, respectively, and declining thereafter, with complete clearance in both organs by day 63 post-inoculation (Figure 3). These data indicate that B. bronchiseptica SigE is not required for colonization or persistence

in the murine respiratory tract. SigE contributes to lethal B. bronchiseptica infection in mice lacking B cells and T cells, but not in mice lacking TLR4 or TNF-α B. bronchiseptica has been observed to cause a range of disease including bronchitis, lethal this website pneumonia, and even systemic infection [11, 12]. Mice with defined immune deficiencies are particularly susceptible to different forms of disease [44–46], facilitating assessment of the roles of specific bacterial factors/functions in interactions with different aspects of the host immune response. Mice lacking key components of innate immunity, either TLR4 or TNF-α, were challenged with RB50 or RB50ΔsigE and signs of severe disease were monitored. Consistent with published studies, TLR4def and TNF-α−/− mice inoculated with 105 CFU of RB50 quickly developed signs of lethal bordetellosis

such as ruffled fur, hunched posture, decreased activity, and difficulty breathing, and succumbed 2 to 5 days post-inoculation [46, 47]. Mice challenged with RB50ΔsigE also ever showed similar signs of disease and time to death (data not shown). In a separate experiment, TLR4def mice and TNF-α−/− mice infected with RB50 or RB50ΔsigE that were still alive by day 3 post-inoculation were dissected for bacterial enumeration in the respiratory as well as systemic organs. Both wild-type and sigE-deficient RB50 colonized the lungs of TLR4def mice at 107-8 CFU, which was almost 1000-fold higher than in the lungs of TLR4suf mice. Moreover, both strains colonized the systemic organs in TLR4def, but not TLR4suf mice (data not shown). Both strains

also grew to higher numbers in the lungs of TNF-α−/− mice than in the lungs of C57BL/6 mice and were recovered from systemic organs only in TNF-α−/− mice (data not shown). These data indicate that SigE is not required for B. bronchiseptica to cause lethal infection and colonize systemic organs in mice lacking TLR4 or TNF-α. B and T cell-deficient Rag1−/− mice succumb to B. bronchiseptica infection, and death is associated with systemic spread of the infection [48]. To assess the role of SigE during infection in hosts deficient in adaptive immunity, groups of Rag1−/− mice were inoculated with 5 × 105 CFU of RB50 or RB50ΔsigE. Rag1−/− mice inoculated with RB50 showed symptoms of lethal bordetellosis on day 13 post-inoculation and succumbed between days 14–35 post-inoculation (Figure 4A).

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