Microbial co-infection alters macrophage polarization, phagosomal escape, and microbial killing

Nikita H. Trivedi; Jieh Juen Yu; Chiung Yu Hung; Richard P. Doelger; Christopher S. Navara; Lisa Y. Armitige; Janakiram Seshu; Anthony P. Sinai; James P. Chambers; M. Neal Guentzel; Bernard P. Arulanandam

doi:10.1177/1753425918760180

Microbial co-infection alters macrophage polarization, phagosomal escape, and microbial killing

Nikita H. Trivedi, Jieh Juen Yu, Chiung Yu Hung, Richard P. Doelger, Christopher S. Navara, Lisa Y. Armitige, Janakiram Seshu, Anthony P. Sinai, James P. Chambers, M. Neal Guentzel, Bernard P. Arulanandam

Microbiology, Immunology, and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection. Non-activated (M0) macrophages or activated M2-polarized cells (J774 cells transfected with the mouse IL-4 gene) were first infected with BCG for 24–48 h, subsequently challenged with LVS, and the results of inhibition of LVS replication in the macrophages was assessed. BCG infection in M0 macrophages activated TLR2-MyD88 and Mincle-CARD9 signaling pathways, stimulating nitric oxide (NO) production and enhanced killing of LVS. BCG infection had little effect on LVS escape from phagosomes into the cytosol in M0 macrophages. In contrast, M2-polarized macrophages exhibited enhanced endosomal acidification, as well as inhibiting LVS replication. Pre-infection with BCG did not induce NO production and thus did not further reduce LVS replication. This study provides a model for studies of the complexity of macrophage activation in response to multi-bacterial infection.

Original language	English
Pages (from-to)	152-162
Number of pages	11
Journal	Innate Immunity
Volume	24
Issue number	3
DOIs	https://doi.org/10.1177/1753425918760180
State	Published - Apr 1 2018

Bibliographical note

Publisher Copyright:
© 2018, © The Author(s) 2018.

Funding

We thank Mr Srikanth Manam and Dr Jilani Chaudry for their technical support for the construction of the J774.vec and J774.IL4 cell lines. We also thank Dr Chinnaswamy Jagannath at the University of Texas Health Science Center at Houston who kindly provided the GFP-expressing BCG under support from his National Institutes of Health (NIH) grant (AI-78420). Image flow analyses were conducted in the University of Texas at San Antonio Immune Defense Core (supported by Research Centers in Minority Institutions, NIH grant G12MD007591). The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: funding from the Army Research Office of the Department of Defense under contract no. W911NF-11-1-0136, and by the Jane and Roland Blumberg Professorship in Biology, to BPA.

Funders	Funder number
Army Research Office of the Department of Defense
The University of Texas Health Science Center at San Antonio
National Institutes of Health (NIH)	AI-78420
National Institutes of Health (NIH)
National Institute on Minority Health and Health Disparities (NIMHD)	G12MD007591
National Institute on Minority Health and Health Disparities (NIMHD)

Keywords

BCG
Francisella
IL-4
co-infection
macrophage

ASJC Scopus subject areas

Microbiology
Immunology
Molecular Biology
Cell Biology
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1177/1753425918760180

Cite this

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title = "Microbial co-infection alters macrophage polarization, phagosomal escape, and microbial killing",

abstract = "Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection. Non-activated (M0) macrophages or activated M2-polarized cells (J774 cells transfected with the mouse IL-4 gene) were first infected with BCG for 24–48 h, subsequently challenged with LVS, and the results of inhibition of LVS replication in the macrophages was assessed. BCG infection in M0 macrophages activated TLR2-MyD88 and Mincle-CARD9 signaling pathways, stimulating nitric oxide (NO) production and enhanced killing of LVS. BCG infection had little effect on LVS escape from phagosomes into the cytosol in M0 macrophages. In contrast, M2-polarized macrophages exhibited enhanced endosomal acidification, as well as inhibiting LVS replication. Pre-infection with BCG did not induce NO production and thus did not further reduce LVS replication. This study provides a model for studies of the complexity of macrophage activation in response to multi-bacterial infection.",

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Microbial co-infection alters macrophage polarization, phagosomal escape, and microbial killing

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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