Differential effects of the Akt pathway on the internalization of Klebsiella by lung epithelium and macrophages

Host response to lung infection includes coordinated efforts of multiple cell types, including the lung epithelium and macrophages. Importantly, both the lung epithelium and macrophages can internalize and clear invading pathogens. However, the mechanisms and their ability to internalize or phagocytose differ. Akt is a key cellular pathway that controls cell proliferation and survival, in addition to its role in host defense. The role of the Akt pathway was assessed using pharmacological Akt modulators in lung epithelial (A549) and macrophage (RAW 264.7) cell lines during Klebsiella bacterial infection. Our data show that the inhibition of the Akt pathway using specific Akt inhibitor MK2206 increased the phagocytic ability of lung epithelial cells but not of macrophages. In contrast, the activation of Akt using specific activator SC-79 decreased the phagocytic ability of epithelial cells, while it increased the phagocytic ability of macrophages. The altered phagocytic ability in both cell types using Akt modulators was not due to changes in bacterial adhesion to the host cell. The clinical usefulness of these Akt modulators may vary based on the type of infection and on the relative contribution of epithelial cells and macrophages in clearing the particular bacterial infection. The Akt pathway has differential roles in the internalization of Klebsiella bacteria by respiratory epithelial cells and immune cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:26

Enthalten in:

Innate immunity - 26(2020), 7 vom: 27. Okt., Seite 618-626

Sprache:

Englisch

Beteiligte Personen:

Chang, De [VerfasserIn]
Feng, Jingjing [VerfasserIn]
Liu, Hongbo [VerfasserIn]
Liu, Wei [VerfasserIn]
Sharma, Lokesh [VerfasserIn]
Dela Cruz, Charles S [VerfasserIn]

Links:

Volltext

Themen:

Akt pathway
EC 2.7.11.1
Epithelial cells
Heterocyclic Compounds, 3-Ring
Journal Article
Klebsiella
MK 2206
Macrophage
Oncogene Protein v-akt
Phagocytosis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 23.09.2021

Date Revised 23.09.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1177/1753425920942582

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM313373558