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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

Chemotaxis of CD3+ (a), CD4+ (b), and CD8+ (c) cells from a healthy subject triggered by conditioned media from M. tb stimulated monocytes. Effect of anti-IL-8, anti-MIP-1α, and anti-MCP-1 antibodies.
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fig7: Chemotaxis of CD3+ (a), CD4+ (b), and CD8+ (c) cells from a healthy subject triggered by conditioned media from M. tb stimulated monocytes. Effect of anti-IL-8, anti-MIP-1α, and anti-MCP-1 antibodies.

Mentions: TB is considered a granulomatous disease due to the accumulation of significant numbers of neutrophils, monocytes, and T lymphocytes in the infected area [2]. However, specific chemokines responsible for recruiting these cells have not yet been identified. We used conditioned media from human monocytes stimulated with heat-killed M. tb to evaluate the contribution of IL-8 to chemotactic responses of T lymphocytes. We noted that monocytes stimulated with M. tb produced approximately 100 ng/mL of IL-8. Conditioned media induced a significant chemotaxis of CD3+, CD4+, and CD8+ T cells. Furthermore, we found that the chemotactic response of T lymphocytes was substantially inhibited by a monoclonal anti-IL-8 antibody (P < 0.05) and not by the control antibody. To examine the possibility that other chemokines, which are produced by the stimulated monocytes, contribute to the migratory activity of the conditioned media, we tested specific neutralizing antibodies against chemokines with known activity towards T cells. These include macrophage inflammatory protein-1α (MIP-1α) and macrophage chemotactic protein-1 (MCP-1). Our results indicated that anti-MIP-1 α antibody or anti-MCP-1 antibody is less effective (P < 0.05) than anti-IL-8 antibody in suppressing the chemotactic response of CD3+ (Figure 7(a)) as well as CD4+ and CD8+ T lymphocytes (Figures 7(b) and 7(c)).


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)

Chemotaxis of CD3+ (a), CD4+ (b), and CD8+ (c) cells from a healthy subject triggered by conditioned media from M. tb stimulated monocytes. Effect of anti-IL-8, anti-MIP-1α, and anti-MCP-1 antibodies.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537748&req=5

fig7: Chemotaxis of CD3+ (a), CD4+ (b), and CD8+ (c) cells from a healthy subject triggered by conditioned media from M. tb stimulated monocytes. Effect of anti-IL-8, anti-MIP-1α, and anti-MCP-1 antibodies.
Mentions: TB is considered a granulomatous disease due to the accumulation of significant numbers of neutrophils, monocytes, and T lymphocytes in the infected area [2]. However, specific chemokines responsible for recruiting these cells have not yet been identified. We used conditioned media from human monocytes stimulated with heat-killed M. tb to evaluate the contribution of IL-8 to chemotactic responses of T lymphocytes. We noted that monocytes stimulated with M. tb produced approximately 100 ng/mL of IL-8. Conditioned media induced a significant chemotaxis of CD3+, CD4+, and CD8+ T cells. Furthermore, we found that the chemotactic response of T lymphocytes was substantially inhibited by a monoclonal anti-IL-8 antibody (P < 0.05) and not by the control antibody. To examine the possibility that other chemokines, which are produced by the stimulated monocytes, contribute to the migratory activity of the conditioned media, we tested specific neutralizing antibodies against chemokines with known activity towards T cells. These include macrophage inflammatory protein-1α (MIP-1α) and macrophage chemotactic protein-1 (MCP-1). Our results indicated that anti-MIP-1 α antibody or anti-MCP-1 antibody is less effective (P < 0.05) than anti-IL-8 antibody in suppressing the chemotactic response of CD3+ (Figure 7(a)) as well as CD4+ and CD8+ T lymphocytes (Figures 7(b) and 7(c)).

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