Table 1.
Virulence Factors Expressed by Two Closely Related Bordetellae
Figure 1.
The Consensus Network of Immunological Steps and Processes Activated upon Invasion by Bordetellae Species
Network nodes denote components of the immune system, and edges represent interactions and processes. Edge labels give a brief biological description of the underlying process. The edges are classified into two regulatory effects, activation and inhibition, and are represented by incoming black arrows and incoming red blunt segments, respectively. Similar notations are used in all network figures.
Table 2.
Boolean Functions Used in the Model
Figure 2.
The Distribution of B. bronchiseptica and B. pertussis Clearance Time Steps in the Completely Asynchronous Model
The frequency (incidence) of bacterial clearance is plotted as a function of the time step of clearance.
Figure 3.
Phase I of In Silico Pathogenesis
Depicts innate immune responses leading to activation of DCs, phagocytes, and PICs during the first week of the infection by B. bronchiseptica or B. pertussis. Bacterial virulence factors are shown as red squares, and edges corresponding to inhibition are in red.
Figure 4.
Phase II of In Silico Pathogenesis
Depicts Th2-related responses, including antibody production and humoral responses to the infection by B. bronchiseptica or B. pertussis infections. Bacterial virulence factors are shown as red squares, and inhibition is denoted by red edges.
Figure 5.
Phase III of In Silico Pathogenesis
Depicts Th1-related responses to the infection by B. bronchiseptica or B. pertussis.
Figure 6.
Growth Curves of the Bacteria in Naive and Convalescent Mice Indicating Three Phases of Pathogenesis
Open triangles represent the experimentally observed mean ± standard error of bacterial number time courses of B. bronchiseptica (top) and B. pertussis (bottom) infection in naive mice. Vertical lines delineate the three pathogenesis phases, which we identify as phase I: innate immune responses (0–7 d); phase II: activation of Th2-related responses and inhibition of Th1-related responses (8–21 d); and phase III: commencement of Th1-related responses and clearance (22–70 d). Open circles represent mean ± standard error of bacterial numbers in a secondary challenge, by the same species, of convalescent mice on day 49 postinoculation with B. bronchiseptica (top) and B. pertussis (bottom). For each case, four mice from each group were killed on the indicated days, and bacterial burden in the lungs was determined. The dotted line denotes the experimental detection limit.
Figure 7.
The Pattern of Activation of Key Nodes in the In Silico Pathogenesis
Comparison of the time course patterns of key nodes (indicated at the left) in mice infected with B. bronchiseptica or B. pertussis in case of WT, TTSS deletion/FHA/ACT deletion, B cell deletion, T0 cell deletion, and for treatment with antibodies prior to infection. Each colored pattern is a square grid representing the state of the nodes on the y-axis versus time steps on the x-axis. The colored squares correspond to active nodes (having state 1) at the time step represented on the x-axis. One time step of the simulation corresponds to 1 d to 2 d of the real infection.
Figure 8.
The Pattern of Activation of Key Nodes during Secondary Infections
Time course patterns of key nodes (y-axis) plotted against time steps (x-axis) during secondary infection by B. bronchiseptica (Bb) and B. pertussis (Bp). One time step corresponds to 1 d to 2 d. The initial state corresponds to the activity of immune system components at the start of the secondary infection. Two scenarios are shown: secondary infection given in phase II of the primary infection (third column), or in phase III of the primary infection (fourth column).