Abstract
Tumor suppressor p53 is involved in regulating immune responses, which contribute to antitumor and antiviral activity. However, whether p53 has anti-bacterial functions remains unclear. Listeria monocytogenes (LM) causes listeriosis in humans and animals, and it is a powerful model for studying innate and adaptive immunity. In the present study, we illustrate an important regulatory role of p53 during LM infection. p53 knockout (p53KO) mice were more susceptible to LM infection, which was manifested by a shorter survival time and lower survival rate. p53KO mice showed significant impairments in LM eradication. Knockdown of p53 in RAW264.7 and HeLa cells resulted in increased invasion and intracellular survival of LM. Furthermore, the invasion and intracellular survival of LM was inhibited in p53-overexpressing RAW264.7 and HeLa cells. LM-infected p53KO mice exhibited severe clinical symptoms and organ injury, presumably because of the abnormal production of the pro-inflammatory cytokines TNF-α, IL-6, IL-12, and IL-18. Decreased IFN-γ and GBP1 productions were observed in LM-infected p53-deficient mice or cells. The combination of these defects likely resulted in the overwhelming LM infection in the p53KO mice. These observations indicate that p53 serves as an important regulator of the host innate immune that protects against LM infection.
Highlights
Newcastle disease virus, and hepatitis C virus[24,25,26,27,28]
We further investigated the pathological changes in the livers and spleens of Listeria monocytogenes (LM)-infected mice. p53 knockout (p53KO) and p53 wild-type (p53WT) mice were infected with a sub-lethal dose of LM
We found that p53KO mice were highly susceptible to LM infection
Summary
This study illustrates an important regulatory role of p53 during LM infection. We found that p53KO mice were highly susceptible to LM infection. Knockdown of p53 expression in RAW264.7 and HeLa cells led to increased susceptible to LM infection These phenomena might be due to the impaired production of IFN-γand GBP1, as well as an abnormal inflammatory response, in p53KO mice. Mice deficient in p53 phenotypically differed from p53WT mice in terms of disease progression, and they exhibited delayed bacterial clearance, an increase in the number of circulating neutrophils, and differential expression patterns of pro-inflammation cytokines. Each of these processes is required for LM resistance. These observations highlight the importance of p53 as an important regulator in the host innate immune that protects against LM, and they provide new insights into the function of p53 in LM infections
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