Abstract Title

FUNCTIONAL REGULATION OF PHAGOCYTIC CELLS BY IL-23 DURING LISTERIA MONOCYTOGENES INFECTION

Presenter Name

Mohanalaxmi Indramohan

Abstract

Listeria monocytogenes (LM) is a Gram-positive intracellular pathogen that causes meningitis and septicemia in immunocompromised individuals, and spontaneous abortion in pregnant women. The versatility of LM makes it a useful tool for immunologists to understand how the immune system responds against harmful microorganisms. Cell recruitment mediated by the IL-23/IL-17 axis is important for protection against infectious diseases, but can cause damage during autoimmune disorders. By utilizing mice lacking IL-23 (IL-23p19 KO), our lab examines the role of this cytokine during a systemic bacterial infection. We have demonstrated that IL-23 promotes resistance against LM infection by increasing the recruitment of neutrophils to the liver, and monocytes to the spleen during LM infection. Interestingly, IL-23 or IL-17A is not required for enhancing phagocytic cell functions including phagocytosis, production of ROS, MPO, and pro-inflammatory mediators during LM infection. Understanding the significance of IL-23/IL-17axis in mediating the recruitment and function of immune cells will aid in the development of effective therapeutics depending on the disease condition.

Purpose (a):

Listeria monocytogenes (LM) is a Gram-positive intracellular foodborne pathogen that causes meningitis and septicemia in immunocompromised individuals, and spontaneous abortion in pregnant women. LM is widely used as a model pathogen to study host pathogen immune interactions. Cell recruitment mediated by the IL-23/IL-17 axis is necessary for protection against multiple infectious diseases, but can be detrimental during autoimmune disorders. We have previously shown utilizing mice lacking IL-23 (IL-23p19 KO) that IL-23 provides protection against LM infection by promoting the optimal recruitment of neutrophils to the liver, and monocytes to the spleen. The receptors for IL-23 and IL-17A are present on phagocytic cells including monocytes, neutrophils, and macrophages. However, it is not known whether IL-23 or IL-17A can impact the function of phagocytic cells during LM infection.

Methods (b):

Splenocytes and liver leukocytes were harvested from mice infected intravenously with ~10, 000 LM. Peritoneal wash was performed to isolate resident peritoneal macrophages. Flow cytometry was utilized to determine phagocytosis, production of reactive oxygen species (ROS), and myeloperoxidase (MPO). The concentrations of TNF-α, IL-1, IL-6, and nitric oxide (NO.) were measured by ELISAs/Griess assay.

Results (c):

Phagocytic cells isolated from control C57Bl/6 (B6) and IL-23p19 KO mice displayed equivalent phagocytic potential. There were no differences in the production of ROS or MPO from splenocytes isolated from both groups of mice. Furthermore, exogenous stimulation with rIL-23 or rIL-17A did not induce or enhance production of ROS or proinflammatory mediators from B6 splenocytes.

Conclusions (d):

IL-23 does not impact the function of phagocytic cells either by a direct or indirect mechanism during LM infection. Collectively, our data suggest that the lack of efficient recruitment of neutrophils to the liver, and monocytes to the spleen, results in a reduction in the overall levels of TNF-α and NO. and therefore, increases the susceptibility of IL-23p19 KO to LM infection.

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FUNCTIONAL REGULATION OF PHAGOCYTIC CELLS BY IL-23 DURING LISTERIA MONOCYTOGENES INFECTION

Listeria monocytogenes (LM) is a Gram-positive intracellular pathogen that causes meningitis and septicemia in immunocompromised individuals, and spontaneous abortion in pregnant women. The versatility of LM makes it a useful tool for immunologists to understand how the immune system responds against harmful microorganisms. Cell recruitment mediated by the IL-23/IL-17 axis is important for protection against infectious diseases, but can cause damage during autoimmune disorders. By utilizing mice lacking IL-23 (IL-23p19 KO), our lab examines the role of this cytokine during a systemic bacterial infection. We have demonstrated that IL-23 promotes resistance against LM infection by increasing the recruitment of neutrophils to the liver, and monocytes to the spleen during LM infection. Interestingly, IL-23 or IL-17A is not required for enhancing phagocytic cell functions including phagocytosis, production of ROS, MPO, and pro-inflammatory mediators during LM infection. Understanding the significance of IL-23/IL-17axis in mediating the recruitment and function of immune cells will aid in the development of effective therapeutics depending on the disease condition.