Research Article: Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen

Date Published: June 14, 2016

Publisher: Public Library of Science

Author(s): Andrew S. Brown, Chao Yang, Ka Yee Fung, Annabell Bachem, Dorothée Bourges, Sammy Bedoui, Elizabeth L. Hartland, Ian R. van Driel, Craig R. Roy.

http://doi.org/10.1371/journal.ppat.1005691

Abstract

Legionella pneumophila is the causative agent of Legionnaires’ disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC), which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity.

Partial Text

Innate immune responses in infected peripheral tissues are essential for controlling invading pathogens in the early phases of infection to prevent rapid pathogen replication and widespread dissemination. Despite this vital role, the main cells and factors that control innate immune responses in tissues are poorly defined. In particular, the innate functions of dendritic cells (DC) in peripheral tissues are not well understood compared to their role as antigen presenting cells in lymphoid organs and the significance of tissue-borne lymphoid cells in peripheral innate immunity has been recognized only recently. Components of the innate immune response to pathogens have mostly been studied in isolation and there are few examples where the interplay between distinct innate components that mediate pathogen clearance in vivo is well understood.

The lung is a major site for potential infection by pathogens. It is therefore important to gain an understanding of the inflammatory milieu in the lung following infection. In this work we examined the cellular interplay following lung infection with L. pneumophila. L. pneumophila is the causative agent of Legionnaires’ disease, a potentially fatal pneumonia that results from environmental exposure to the bacteria. Upon entering the lung, L. pneumophila replicates inside alveolar macrophages. Intracellular replication requires the bacterial Dot/Icm type IV secretion system to inject bacterial effector proteins into the macrophage cytosol, which establishes a ‘Legionella containing vacuole’ permissive for bacterial replication [10,11,41].

 

Source:

http://doi.org/10.1371/journal.ppat.1005691

 

0 0 vote
Article Rating
Subscribe
Notify of
guest
0 Comments
Inline Feedbacks
View all comments