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Binding of CXCL8/IL-8 to Mycobacterium tuberculosis Modulates the Innate Immune Response.

Krupa A, Fol M, Dziadek BR, Kepka E, Wojciechowska D, Brzostek A, Torzewska A, Dziadek J, Baughman RP, Griffith D, Kurdowska AK - Mediators Inflamm. (2015)

Bottom Line: In addition, we have shown that significant amount of IL-8 present in the blood of TB patients associates with erythrocytes.Finally, we have noted that IL-8 is the major chemokine responsible for recruiting T lymphocytes (CD3(+), CD4(+), and CD8(+) T cells).In summary, our data suggest that the association of IL-8 with M. tb molecules may modify and possibly enhance the innate immune response in patients with TB.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA ; Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland.

ABSTRACT
Interleukin-8 (IL-8) has been implicated in the pathogenesis of several human respiratory diseases, including tuberculosis (TB). Importantly and in direct relevance to the objectives of this report quite a few findings suggest that the presence of IL-8 may be beneficial for the host. IL-8 may aid with mounting an adequate response during infection with Mycobacterium tuberculosis (M. tb); however, the underlying mechanism remains largely unknown. The major goal of our study was to investigate the contribution of IL-8 to the inflammatory processes that are typically elicited in patients with TB. We have shown for the first time that IL-8 can directly bind to tubercle bacilli. We have also demonstrated that association of IL-8 with M. tb molecules leads to the augmentation of the ability of leukocytes (neutrophils and macrophages) to phagocyte and kill these bacilli. In addition, we have shown that significant amount of IL-8 present in the blood of TB patients associates with erythrocytes. Finally, we have noted that IL-8 is the major chemokine responsible for recruiting T lymphocytes (CD3(+), CD4(+), and CD8(+) T cells). In summary, our data suggest that the association of IL-8 with M. tb molecules may modify and possibly enhance the innate immune response in patients with TB.

No MeSH data available.


Related in: MedlinePlus

Respiratory burst presented as a level of pp40phox component detected using fluorescent microscopy. (a) Level of pp40phox molecule in neutrophils infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells. (b) Level of pp40phox molecule in THP-1 cells infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells.
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fig5: Respiratory burst presented as a level of pp40phox component detected using fluorescent microscopy. (a) Level of pp40phox molecule in neutrophils infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells. (b) Level of pp40phox molecule in THP-1 cells infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells.

Mentions: The protein p40phox is a major constituent of NADPH-oxidase, which is a multicomponent enzyme system responsible for the oxidative burst [31, 32]. As a consequence of stimulation of inflammatory cells p40phox is phosphorylated and translocates from the cytosol to the cell membrane to form an enzymatic complex which produces oxygen radicals. Analysis of the level of phospho-p40phox in neutrophils and THP-1 derived macrophages infected with M. tb was performed using fluorescent microscopy. As shown in Figure 5(a), the presence of IL-8 associated with M. tb molecules caused the increase (approximately 1.38 times) in the level of pp40phox in neutrophils compared to chemokine-free bacteria but the difference was not statistically significant (P = 0.28). Similar observations were made using THP-1 derived macrophages stimulated with IL-8 coated or uncoated M. tb cells (Figure 5(b)). Analysis of fluorescence intensity showed that cells infected with M. tb opsonized with IL-8 appeared to be more potent (1.57 times) producers of phospho-p40phox (P < 0.001; Figure 5(b)).


Binding of CXCL8/IL-8 to Mycobacterium tuberculosis Modulates the Innate Immune Response.

Krupa A, Fol M, Dziadek BR, Kepka E, Wojciechowska D, Brzostek A, Torzewska A, Dziadek J, Baughman RP, Griffith D, Kurdowska AK - Mediators Inflamm. (2015)

Respiratory burst presented as a level of pp40phox component detected using fluorescent microscopy. (a) Level of pp40phox molecule in neutrophils infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells. (b) Level of pp40phox molecule in THP-1 cells infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4537748&req=5

fig5: Respiratory burst presented as a level of pp40phox component detected using fluorescent microscopy. (a) Level of pp40phox molecule in neutrophils infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells. (b) Level of pp40phox molecule in THP-1 cells infected with M. tb cytokine-free (M. tb) or M. tb associated with IL-8 (M. tb/IL-8) presented as an intensity scan/increase fold over normal cells.
Mentions: The protein p40phox is a major constituent of NADPH-oxidase, which is a multicomponent enzyme system responsible for the oxidative burst [31, 32]. As a consequence of stimulation of inflammatory cells p40phox is phosphorylated and translocates from the cytosol to the cell membrane to form an enzymatic complex which produces oxygen radicals. Analysis of the level of phospho-p40phox in neutrophils and THP-1 derived macrophages infected with M. tb was performed using fluorescent microscopy. As shown in Figure 5(a), the presence of IL-8 associated with M. tb molecules caused the increase (approximately 1.38 times) in the level of pp40phox in neutrophils compared to chemokine-free bacteria but the difference was not statistically significant (P = 0.28). Similar observations were made using THP-1 derived macrophages stimulated with IL-8 coated or uncoated M. tb cells (Figure 5(b)). Analysis of fluorescence intensity showed that cells infected with M. tb opsonized with IL-8 appeared to be more potent (1.57 times) producers of phospho-p40phox (P < 0.001; Figure 5(b)).

Bottom Line: In addition, we have shown that significant amount of IL-8 present in the blood of TB patients associates with erythrocytes.Finally, we have noted that IL-8 is the major chemokine responsible for recruiting T lymphocytes (CD3(+), CD4(+), and CD8(+) T cells).In summary, our data suggest that the association of IL-8 with M. tb molecules may modify and possibly enhance the innate immune response in patients with TB.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, TX 75708, USA ; Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland.

ABSTRACT
Interleukin-8 (IL-8) has been implicated in the pathogenesis of several human respiratory diseases, including tuberculosis (TB). Importantly and in direct relevance to the objectives of this report quite a few findings suggest that the presence of IL-8 may be beneficial for the host. IL-8 may aid with mounting an adequate response during infection with Mycobacterium tuberculosis (M. tb); however, the underlying mechanism remains largely unknown. The major goal of our study was to investigate the contribution of IL-8 to the inflammatory processes that are typically elicited in patients with TB. We have shown for the first time that IL-8 can directly bind to tubercle bacilli. We have also demonstrated that association of IL-8 with M. tb molecules leads to the augmentation of the ability of leukocytes (neutrophils and macrophages) to phagocyte and kill these bacilli. In addition, we have shown that significant amount of IL-8 present in the blood of TB patients associates with erythrocytes. Finally, we have noted that IL-8 is the major chemokine responsible for recruiting T lymphocytes (CD3(+), CD4(+), and CD8(+) T cells). In summary, our data suggest that the association of IL-8 with M. tb molecules may modify and possibly enhance the innate immune response in patients with TB.

No MeSH data available.


Related in: MedlinePlus