Dataset Information

Susceptibility to Plasmodium yoelii preerythrocytic infection in BALB/c substrains is determined at the point of hepatocyte invasion.

ABSTRACT: After transmission by Anopheles mosquitoes, Plasmodium sporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (LS). Rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between strains of mice. This has been mainly attributed to differences in innate immune responses and parasite infectivity. Here, we report that BALB/cByJ mice are more susceptible to Plasmodium yoelii preerythrocytic infection than BALB/cJ mice. This difference occurs at the level of early hepatocyte infection, but expression levels of reported host factors that are involved in infection do not correlate with susceptibility. Interestingly, BALB/cByJ hepatocytes are more frequently polyploid; thus, their susceptibility converges on the previously observed preference of sporozoites to infect polyploid hepatocytes. Gene expression analysis demonstrates hepatocyte-specific differences in mRNA abundance for numerous genes between BALB/cByJ and BALB/cJ mice, some of which encode hepatocyte surface molecules. These data suggest that a yet-unknown receptor for sporozoite infection, present at elevated levels on BALB/cByJ hepatocytes and also polyploid hepatocytes, might facilitate Plasmodium liver infection.

SUBMITTER: Kaushansky A

PROVIDER: S-EPMC4288894 | biostudies-other | 2015 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Susceptibility to Plasmodium yoelii preerythrocytic infection in BALB/c substrains is determined at the point of hepatocyte invasion.

Kaushansky Alexis A Austin Laura S LS Mikolajczak Sebastian A SA Lo Fang Y FY Miller Jessica L JL Douglass Alyse N AN Arang Nadia N Vaughan Ashley M AM Gardner Malcolm J MJ Kappe Stefan H I SH

Infection and immunity 20141013 1

After transmission by Anopheles mosquitoes, Plasmodium sporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (LS). Rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between strains of mice. This has been mainly attributed to differences in innate immune responses and parasite infectivity. Here, we report that BALB/cByJ mice are more susceptible to Plasmodium yoelii preeryth ...[more]

PMID: 25312960

Similar Datasets

Project description:Malaria and tuberculosis (Tb) are two of the main causes of death from infectious diseases globally. The pathogenic agents, Plasmodium parasites and Mycobacterium tuberculosis, are co-endemic in many regions in the world, however, compared to other co-infections like HIV/Tb or helminth/Tb, malaria/Tb has been given less attention both in clinical and immunological studies. Due to the lack of sufficient human data, the impact of malaria on Tb and vice versa is difficult to estimate but co-infections are likely to occur very frequently. Due to its immunomodulatory properties malaria might be an underestimated risk factor for latent or active Tb patients particularly in high-endemic malaria settings were people experience reinfections very frequently. In the present study, we used the non-lethal strain of Plasmodium yoelii to investigate, how one episode of self-resolving malaria impact on a chronic M. tuberculosis infection. P. yoelii co-infection resulted in exacerbation of Tb disease as demonstrated by increased pathology and cellular infiltration of the lungs which coincided with elevated levels of pro- and anti-inflammatory mediators. T cell responses were not impaired in co-infected mice but enhanced and likely contributed to increased cytokine production. We found a slight but statistically significant increase in M. tuberculosis burden in co-infected animals and increased lung CFU was positively correlated with elevated levels of TNF? but not IL-10. Infection with P. yoelii induced the recruitment of a CD11c(+) population into lungs and spleens of M. tuberculosis infected mice. CD11c(+) cells isolated from P. yoelii infected spleens promoted survival and growth of M. tuberculosis in vitro. 170 days after P. yoelii infection changes in immunopathology and cellular immune responses were no longer apparent while M. tuberculosis numbers were still slightly higher in lungs, but not in spleens of co-infected mice. In conclusion, one episode of P. yoelii co-infection transiently exacerbated disease severity but had no long-term consequences on disease progression and survival of M. tuberculosis infected mice.

Dataset Information

Susceptibility to Plasmodium yoelii preerythrocytic infection in BALB/c substrains is determined at the point of hepatocyte invasion.

Publications

Susceptibility to Plasmodium yoelii preerythrocytic infection in BALB/c substrains is determined at the point of hepatocyte invasion.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure