The Role of Alveolar Epithelial Cells in Initiating and Shaping Pulmonary Immune Responses: Communication between Innate and Adaptive Immune Systems

Olga D Chuquimia,Dagbjort H Petursdottir,Katharina Hartl,Mahavir Singh,Muhammad J Rahman,Carmen Fernández,Dennis W Metzger

doi:10.1371/journal.pone.0032125

Olga D Chuquimia, Dagbjort H Petursdottir + Show 5 more

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https://doi.org/10.1371/journal.pone.0032125

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Abstract

Macrophages and dendritic cells have been recognized as key players in the defense against mycobacterial infection. However, more recently, other cells in the lungs such as alveolar epithelial cells (AEC) have been found to play important roles in the defense and pathogenesis of infection. In the present study we first compared AEC with pulmonary macrophages (PuM) isolated from mice in their ability to internalize and control Bacillus Calmette-Guérin (BCG) growth and their capacity as APCs. AEC were able to internalize and control bacterial growth as well as present antigen to primed T cells. Secondly, we compared both cell types in their capacity to secrete cytokines and chemokines upon stimulation with various molecules including mycobacterial products. Activated PuM and AEC displayed different patterns of secretion. Finally, we analyzed the profile of response of AEC to diverse stimuli. AEC responded to both microbial and internal stimuli exemplified by TLR ligands and IFNs, respectively. The response included synthesis by AEC of several factors, known to have various effects in other cells. Interestingly, TNF could stimulate the production of CCL2/MCP-1. Since MCP-1 plays a role in the recruitment of monocytes and macrophages to sites of infection and macrophages are the main producers of TNF, we speculate that both cell types can stimulate each other. Also, another cell-cell interaction was suggested when IFNs (produced mainly by lymphocytes) were able to induce expression of chemokines (IP-10 and RANTES) by AEC involved in the recruitment of circulating lymphocytes to areas of injury, inflammation, or viral infection. In the current paper we confirm previous data on the capacity of AEC regarding internalization of mycobacteria and their role as APC, and extend the knowledge of AEC as a multifunctional cell type by assessing the secretion of a broad array of factors in response to several different types of stimuli.

Highlights

Tuberculosis (TB) is still one of the most devastating diseases affecting both humans and animals [1,2]
Even if pulmonary macrophages (PuM) displayed a higher capacity than alveolar epithelial cells (AEC), our results demonstrated that AEC were able to internalize mycobacteria as assessed by microscopy (Figure 2) and relative luminescence units (RLU) determinations Table 1 (AEC: 195637 versus PuM: 676694)
Even if in our AEC population only 70% of the cells were AEC II, we addressed this question by testing the ability of AEC and PuM pulsed for 24 h with the mycobacterial antigen 19 kDa (AEC19 kDa and PuM19 kDa, respectively) to present antigen to T cells primed with the same antigen

Summary

Introduction

Tuberculosis (TB) is still one of the most devastating diseases affecting both humans and animals [1,2]. Interactions between mycobacteria and different host target cells in the respiratory mucosa, dictate the outcome of mycobacterial infection in man ranging from an asymptomatic infection to a life-threatening disease. In these interactions both innate and adaptive immune responses play critical roles. Disease can be prevented in two ways; a) the innate immune system alone can be able to impede bacterial invasion and infection, b) if infection takes place, two alternatives can occur, either the host adaptive immune system is able to control bacterial replication or it will fail in this process. The identification of the mechanisms controlling Mtb adaptation to the intracellular environment remains to be solved

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