Listeria ivanovii Infection in Mice: Restricted to the Liver and Lung with Limited Replication in the Spleen

Abstract

Listeria monocytogenes (LM) vectors have shown much promise in delivery of viral and tumor antigens for the development of vaccines. L. ivanovii (LI) is a closely related bacterium with a similar intracellular life cycle that may offer advantages over LM because it is not a human pathogen, but can infect other animal species. Recent studies show that recombinant LI expressing Mycobacterium tuberculosis antigens is effective in inducing protective immunity in mouse models, demonstrating the potential of LI as a live vaccine vector. However, a key barrier in the development of LI into a live vaccine vector is that its pathogenic and immunogenic characteristics have yet to be fully understood. Therefore, in this research, C57BL/6J mice were inoculated with LM or LI intravenously or intranasally, and bacterial loads, histopathologic changes, and cytokine production were determined at indicated days post inoculation. Results showed that after intravenous infection with LM or LI, bacteria were found proliferating in the liver, spleen, and lung. However, LI could only reach a heavy burden in the liver and its ability to multiply and to resist host immunity seemed limited in the spleen and lung. After intranasal inoculation with LI, bacteria were mainly localized in the lung and failed to infect liver or spleen, while LM could. In organs with heavy LI burden, lesions were isolated, localized and densely packed, compared to lesions caused by LM, which were invasive. In the liver of intravenously inoculated mice and lung of intranasally inoculate mice, LI was able to elicit comparable cytokine production with LM and cause less severe histopathologic damages, and thus could be considered as a vector for treating or preventing hepatic or pulmonary diseases.

Intranasal vaccination with Listeria ivanovii as vector of Mycobacterium tuberculosis antigens promotes specific lung-localized cellular and humoral immune responses

“…It is not surprising that both strains failed to induce antigen-specific cellular immunity in the spleen because they did not establish a durable infection in the spleen. As we reported previously, when LI invaded the lung via the respiratory tract, the typical infection lesions that resulted seemed isolated and densely packed 18 . This phenomenon can be attributed to the unique feature of ivanolysin O (ILO).…”

“…After intravenous administration, bacteria were delivered via circulation of the blood and directly entered peripheral immune organs such as the spleen and liver, where they were phagocytosed by phagocytes and dendritic cells, thus inducing efficient systemic immune responses 17 . Our earlier studies showed that wild-type LI mainly localized in the lung after intranasal administration 18 . Therefore, LIΔ-Rv3875 and LIΔ-Rv0129c elicited lung-localized antigen-specific T cell immune responses www.nature.com/scientificreports www.nature.com/scientificreports/ and pulmonary mucosal SIgA.…”

“…A total of 2.5 × 10 6 lung cells or splenocytes were added to 96-well microplates. Cells from LIΔ-Rv3875-infected mice and from LIΔ-Rv0129c-infected mice were stimulated with ESAT-6 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] or Ag85C peptide complex (Ag85C and Ag85C 81-100 ), respectively, at 37 °C and 5% CO 2 for 4 h. Cells from the LIΔ and NS groups were stimulated with a mixture of all of the above mentioned peptides. For www.nature.com/scientificreports www.nature.com/scientificreports/ each well, the corresponding unstimulated cell well served as a blank control.…”

“…Our previous studies showed that LI infection in mice is restricted to the lung after intranasal administration 18 , which leads us to hypothesize that LI might be a potential vaccine vector for developing vaccines against pulmonary infections. Investigating the ability of recombinant LI strains integrated with heterologous antigens to induce immune responses via intranasal vaccination is valuable in evaluating LI as a good antigen delivery vehicle for vaccines against respiratory tract infections.…”

Prevalence and Characteristics of Listeria ivanovii Strains in Wild Rodents in China

“…In recent years, some countries have regular monitoring of L. monocytogenes and the research orientation also extend to more fields with some outbreaks of foodborne infections by L. monocytogenes being reported (Gillesberg Lassen et al 2016). L. ivanovii is associated with abortion in ruminants, especially sheep, and has the ability to cause severe clinical symptoms, such as bacteremia, mesenteric adenitis, uterine discharge, and stillbirth, but does not cause encephalitis (González-Zorn et al 1999, Ramage et al 1999, Guillet et al 2010, Beye et al 2016, Zhou et al 2016. L. ivanovii has also been reported to cause human listeriosis (Guillet et al 2010, Beye et al 2016.…”