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Blocking of integrins inhibits HIV-1 infection of human cervical mucosa immune cells with free and complement-opsonized virions.

Tjomsland V, Ellegård R, Kjölhede P, Wodlin NB, Hinkula J, Lifson JD, Larsson M - Eur. J. Immunol. (2013)

Bottom Line: Blockage of the α4-, β7-, and β1-integrins significantly inhibited HIV-1 infection of both DCs and CD4(+) T cells.We found a greater impairment of HIV-1 infection in DCs for complement-opsonized virions compared with that of free virions when αM/β2- and α4-integrins were blocked.We show that blocking of integrins decreases the HIV-1 infection of both mucosal DCs and CD4(+) T cells emigrating from the cervical tissues.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

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Blockade of the C-type lectin MMR decreases the infection of DCs emigrating out from cervical tissues. The cervical tissue biopsies were pretreated for 30 min at min 37°C with mock, mannan, anti-MMR mAb, or isotype control mAb followed by infection with different forms of HIV-1BaL, either free (F-HIV) or complement opsonized (C-HIV), by spinning the cultures for 2 h at 37°C. The tissues were washed and transferred to six-well plates and cultured for 3–6 days with mock, mannan, anti-MMR mAb, or isotype control mAb. The emigrating cells were harvested and stained with anti-CD1a, and anti-HIV-1 mAbs for DCs and anti-CD3, anti-CD4, and anti-HIV-1 mAbs for CD4+ T cells and level of infection was assessed by flow cytometry. (A, B) The level of HIV-1 infection in (A) DCs (N = 4–5) or (B) T cells (N = 3) in the different experiments treated with mock or mannan was normalized with F-HIV set as 100%. (C, D) The level of HIV-1 infection in (C) DCs (N = 4–7) or (D) T cells (N = 4–9) in the different experiments treated with mock, anti-MMR mAb, or isotype control mAb was normalized with F-HIV set as 100%. Statistical significance was tested using a two-sided paired t-test. *p < 0.05, **p < 0.001, ***p < 0.0001. Data are shown as mean + SEM of the indicated number of samples, each assessed in its own experiment.
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fig04: Blockade of the C-type lectin MMR decreases the infection of DCs emigrating out from cervical tissues. The cervical tissue biopsies were pretreated for 30 min at min 37°C with mock, mannan, anti-MMR mAb, or isotype control mAb followed by infection with different forms of HIV-1BaL, either free (F-HIV) or complement opsonized (C-HIV), by spinning the cultures for 2 h at 37°C. The tissues were washed and transferred to six-well plates and cultured for 3–6 days with mock, mannan, anti-MMR mAb, or isotype control mAb. The emigrating cells were harvested and stained with anti-CD1a, and anti-HIV-1 mAbs for DCs and anti-CD3, anti-CD4, and anti-HIV-1 mAbs for CD4+ T cells and level of infection was assessed by flow cytometry. (A, B) The level of HIV-1 infection in (A) DCs (N = 4–5) or (B) T cells (N = 3) in the different experiments treated with mock or mannan was normalized with F-HIV set as 100%. (C, D) The level of HIV-1 infection in (C) DCs (N = 4–7) or (D) T cells (N = 4–9) in the different experiments treated with mock, anti-MMR mAb, or isotype control mAb was normalized with F-HIV set as 100%. Statistical significance was tested using a two-sided paired t-test. *p < 0.05, **p < 0.001, ***p < 0.0001. Data are shown as mean + SEM of the indicated number of samples, each assessed in its own experiment.

Mentions: To study the impact of C-type lectins on infection in DCs and CD4+ T cells, we exposed cervical mucosa to the mannose polymer mannan, a competing ligand for C-type lectins, before challenging the tissues with HIV-1. Infection was decreased for both F-HIV (46%, p = 0.005) and C-HIV (40%, p = 0.023) in emigrating DCs after blocking C-type lectins located in the cervical mucosa (Fig. 4A). In contrast, no effect on the infection of emigrating CD4+ T cells was observed (Fig. 4B). DCs emigrating from cervical tissues have been shown to express MMR 24. Blocking this C-type lectin using anti-MMR mAb gave similar results as when C-type lectins were blocked using mannan with a 51% (p = 0.006) decrease in F-HIV infection in DCs (Fig. 4C). When the cervical tissue was challenged with C-HIV, the corresponding decrease in DC infection was 43% (p = 0.029) (Fig. 4C). As expected, infection of CD4+ T cells was not affected by blocking MMR in the cervical mucosa (Fig. 4D). Blocking of MMR had a slightly higher effect on DC infection with F-HIV than with C-HIV.


Blocking of integrins inhibits HIV-1 infection of human cervical mucosa immune cells with free and complement-opsonized virions.

Tjomsland V, Ellegård R, Kjölhede P, Wodlin NB, Hinkula J, Lifson JD, Larsson M - Eur. J. Immunol. (2013)

Blockade of the C-type lectin MMR decreases the infection of DCs emigrating out from cervical tissues. The cervical tissue biopsies were pretreated for 30 min at min 37°C with mock, mannan, anti-MMR mAb, or isotype control mAb followed by infection with different forms of HIV-1BaL, either free (F-HIV) or complement opsonized (C-HIV), by spinning the cultures for 2 h at 37°C. The tissues were washed and transferred to six-well plates and cultured for 3–6 days with mock, mannan, anti-MMR mAb, or isotype control mAb. The emigrating cells were harvested and stained with anti-CD1a, and anti-HIV-1 mAbs for DCs and anti-CD3, anti-CD4, and anti-HIV-1 mAbs for CD4+ T cells and level of infection was assessed by flow cytometry. (A, B) The level of HIV-1 infection in (A) DCs (N = 4–5) or (B) T cells (N = 3) in the different experiments treated with mock or mannan was normalized with F-HIV set as 100%. (C, D) The level of HIV-1 infection in (C) DCs (N = 4–7) or (D) T cells (N = 4–9) in the different experiments treated with mock, anti-MMR mAb, or isotype control mAb was normalized with F-HIV set as 100%. Statistical significance was tested using a two-sided paired t-test. *p < 0.05, **p < 0.001, ***p < 0.0001. Data are shown as mean + SEM of the indicated number of samples, each assessed in its own experiment.
© Copyright Policy - open-access
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fig04: Blockade of the C-type lectin MMR decreases the infection of DCs emigrating out from cervical tissues. The cervical tissue biopsies were pretreated for 30 min at min 37°C with mock, mannan, anti-MMR mAb, or isotype control mAb followed by infection with different forms of HIV-1BaL, either free (F-HIV) or complement opsonized (C-HIV), by spinning the cultures for 2 h at 37°C. The tissues were washed and transferred to six-well plates and cultured for 3–6 days with mock, mannan, anti-MMR mAb, or isotype control mAb. The emigrating cells were harvested and stained with anti-CD1a, and anti-HIV-1 mAbs for DCs and anti-CD3, anti-CD4, and anti-HIV-1 mAbs for CD4+ T cells and level of infection was assessed by flow cytometry. (A, B) The level of HIV-1 infection in (A) DCs (N = 4–5) or (B) T cells (N = 3) in the different experiments treated with mock or mannan was normalized with F-HIV set as 100%. (C, D) The level of HIV-1 infection in (C) DCs (N = 4–7) or (D) T cells (N = 4–9) in the different experiments treated with mock, anti-MMR mAb, or isotype control mAb was normalized with F-HIV set as 100%. Statistical significance was tested using a two-sided paired t-test. *p < 0.05, **p < 0.001, ***p < 0.0001. Data are shown as mean + SEM of the indicated number of samples, each assessed in its own experiment.
Mentions: To study the impact of C-type lectins on infection in DCs and CD4+ T cells, we exposed cervical mucosa to the mannose polymer mannan, a competing ligand for C-type lectins, before challenging the tissues with HIV-1. Infection was decreased for both F-HIV (46%, p = 0.005) and C-HIV (40%, p = 0.023) in emigrating DCs after blocking C-type lectins located in the cervical mucosa (Fig. 4A). In contrast, no effect on the infection of emigrating CD4+ T cells was observed (Fig. 4B). DCs emigrating from cervical tissues have been shown to express MMR 24. Blocking this C-type lectin using anti-MMR mAb gave similar results as when C-type lectins were blocked using mannan with a 51% (p = 0.006) decrease in F-HIV infection in DCs (Fig. 4C). When the cervical tissue was challenged with C-HIV, the corresponding decrease in DC infection was 43% (p = 0.029) (Fig. 4C). As expected, infection of CD4+ T cells was not affected by blocking MMR in the cervical mucosa (Fig. 4D). Blocking of MMR had a slightly higher effect on DC infection with F-HIV than with C-HIV.

Bottom Line: Blockage of the α4-, β7-, and β1-integrins significantly inhibited HIV-1 infection of both DCs and CD4(+) T cells.We found a greater impairment of HIV-1 infection in DCs for complement-opsonized virions compared with that of free virions when αM/β2- and α4-integrins were blocked.We show that blocking of integrins decreases the HIV-1 infection of both mucosal DCs and CD4(+) T cells emigrating from the cervical tissues.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Show MeSH
Related in: MedlinePlus