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- Chuquimia, Olga D., 1977-, et al.
(författare)
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Alveolar epithelial cells are critical in protection of the respiratory tract by secretion of factors able to modulate the activity of pulmonary macrophages and directly control bacterial growth
- 2013
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 81:1, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- The respiratory epithelium is a physical and functional barrier actively involved in the clearance of environmental agents. The alveolar compartment is lined with membranous pneumocytes known as type I alveolar epithelial cells (AEC I), and granular pneumocytes, type II alveolar epithelial cells (AEC II). AEC II are responsible for epithelial reparation upon injury and ion transport and are very active immunologically contributing to lung defense by secreting antimicrobial factors. AEC II also secrete a broad variety of factors such as cytokines and chemokines involved in activation and differentiation of immune cells and are able to present antigen to specific T cells. Another cell type important in lung defense is the pulmonary macrophage (PuM). Considering the architecture of the alveoli, a good communication between the external and the internal compartments is crucial to mount effective responses. Our hypothesis is that being in the interface; AEC may play an important role in transmitting signals from the external to the internal compartment and in modulating the activity of PuM. For this, we collected supernatants from AEC unstimulated or stimulated in vitro with lipopolysaccharide (LPS). These AEC-conditioned media were used in various setups to test for the effect on a number of macrophage functions: a) migration; b) phagocytosis and intracellular control of bacterial growth and c) phenotypic changes and morphology. Finally, we tested the direct effect of AEC-conditioned media on bacterial growth. We found that AEC-secreted factors had a dual effect, in one hand controlling bacterial growth and on the other hand increasing macrophage activity.
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| 2. |
- Rahman, Muhammad J, et al.
(författare)
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Impact of Toll-like receptor 2 deficiency on immune responses to mycobacterial antigens
- 2011
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 79:11, s. 4649-4656
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, we addressed the question of whether Toll-like receptor 2 (TLR2)-mediated innate immunity can contribute to the development of acquired immune responses. We immunized TLR2(-/-) and wild-type (WT) mice three times subcutaneously with the mycobacterial antigen (Ag19kDa) (a TLR2 ligand) or Ag85A (not a TLR2 ligand). One week after the last immunization, sera and spleens were collected. To evaluate cellular responses, we measured gamma interferon (IFN-γ) after in vitro restimulation of spleen cells with antigen alone or antigen-pulsed bone marrow-derived macrophages (BMM(Ag)) or pulmonary macrophages (PuM(Ag)). Antibody responses were comparable in the two mouse strains, but we observed differences in the cellular responses. Recall responses to Ag85A were similar in the two strains, but responses to Ag19kDa given alone or presented by BMM or PuM were lower in TLR2(-/-) than in WT mice. The largest differences in cellular responses were observed when Ag19kDa was presented by PuM. To understand this, we analyzed phenotypic and functional differences between BMM and PuM upon stimulation with various ligands. Generally, PuM had a lower response to the TLR2 ligand Pam(3)Cys-Ser-(Lys)(4) trihydrochloride and to anti-CD40 than BMM, as measured by cytokine secretion and upregulation of costimulatory molecules. This might provide a partial explanation for the lower capacity of PuM when pulsed with Ag19kDa, also a TLR2 ligand. Altogether, our results revealed weaknesses in the T cell and antigen-presenting cell (APC) compartments of the Ag19kDa-immunized TLR2(-/-) mice but indicated that specific immune responses could be generated in the absence of TLR2 regardless of the characteristics of the antigen used.
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