Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain

Abstract

BackgroundMice are a natural host for Rodentibacter (R.) pneumotropicus. Despite specific monitoring, it is still one of the most important infectious agents in laboratory animals. The objective of this study was to determine the virulence of a prevalent pathotype of R. pneumotropicus and characterize the host response in a new animal model.ResultsIntranasal infection of C57BL/6 and BALB/c mice with a R. pneumotropicus strain (JF4Ni) bearing the genes of the three known repeats in toxin (RTX) toxins resulted in an unprecedented high mortality and morbidity above 50 and 80%, respectively. Morbidity was associated with severe weight loss as well as conjunctivitis and dyspnea. A main pathology was a catarrhal purulent to necrotic bronchopneumonia. Specific immune globuline (Ig) A was detected in tracheonasal lavages of most surviving mice which were still colonized by R. pneumotropicus. Furthermore, all surviving animals showed a distinct production of IgG antibodies. To differentiate T-helper cell (Th) 1 and Th2 immune responses we used subclasses of IgGs as indicators. Mean ratios of IgG2b to IgG1 were below 0.8 in sera drawn from both mice strains prior infection and from BALB/c mice post infection. In contrast, C57BL/6 mice had a mean IgG2b/IgG1 ratio of 1.6 post infection indicating a Th1 immune response in C57BL/6 versus a Th2 response in BALB/c mice associated with a tenfold higher bacterial load in the lung. In accordance with a Th1 response high antigen-specific IgG2c titers were detected in the majority of surviving C57BL/6 mice.ConclusionsR. pneumotropicus JF4Ni is a highly virulent strain causing severe pneumonia and septicemia after intranasal infection of C57BL/6 and BALB/c mice. Persisting infections in the two mice strains are associated with Th1 and Th2 immune responses, respectively, and differences in the bacterial burden of the lung. The described model is ideally suited for future vaccination studies using the natural host.Electronic supplementary materialThe online version of this article (10.1186/s12866-018-1186-8) contains supplementary material, which is available to authorized users.

Low-Energy Electron Irradiation Efficiently Inactivates the Gram-Negative Pathogen Rodentibacter pneumotropicus—A New Method for the Generation of Bacterial Vaccines with Increased Efficacy

“…The R. pneumotropicus strain JF4Ni used in this study has been described previously [19]. In brief, bacteria were grown overnight in a Brain Heart Infusion (BHI) medium (Carl Roth) at 37 • C and rotation at 200 rpm.…”

“…The wells were blocked with PBS containing 5% skim milk. For the detection of antigens, a pool of polyclonal mouse sera drawn from reconvalescent mice experimentally infected with R. pneumotropicus strain JF4Ni [19] was used at a 1:800 dilution. The polyclonal sera were added and incubated for 2 h at room temperature.…”

“…To test whether the immunization with inactivated R. pneumotropicus protected against infection of the lower respiratory tract, immunized and control mice were challenged with R. pneumotropicus (strain JF4Ni), and the clinical score was analyzed. Due to the high morbidity and mortality observed in previous experiments with this particular strain [19], we decided to use a sub-lethal dose of 6 × 10 6 CFU per animal. None of the vaccinated mice showed a clinical score above 1 after infection, while five out of nine non-vaccinated animals had a cumulative clinical score of 2, which corresponded to a mean loss of body weight of more than 5%.…”

“…Although these Gram-negative bacteria are part of the microbiome of the respiratory tract, they can cause primary or secondary infections, often leading to severe diseases. Experimental infection of wild-type mice with a highly virulent R. pneumotropicus strain [19] represents a useful model for improving vaccination strategies against invasive Gram-negative bacteria, even more so as members of the Pasteurellaceae exhibit a high degree of host adaptation. We show here that LEEI can be used to inactivate R. pneumotropicus and that the irradiated material induces protective immunity.…”

Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis

“…Our data indicated that Rodentibacter are prime candidates contributing to hamster VL progression. This genus includes rodent pathobiont species that can cause opportunistic infections, septicaemia and severe pneumonia [42,43]. L. donovani infection of the intestinal mucosa may be directly related to the increased gut barrier permeability observed during progressive disease, similar to that produced by enteropathogens and other systemic infections (reviewed in [44]).…”