TY - JOUR
T1 - CXCR3 and IFN protein-10 in Pneumocystis pneumonia
AU - McAllister, Florencia
AU - Ruan, Sanbao
AU - Steele, Chad
AU - Zheng, Mingquan
AU - McKinley, Laura
AU - Ulrich, Lauren
AU - Marrero, Luis
AU - Shellito, Judd E.
AU - Kolls, Jay K.
PY - 2006/8/1
Y1 - 2006/8/1
N2 - We have previously shown that Tc1 CD8+ T cells have in vitro and in vivo effector activity against Pneumocystis (PC) infection in mice. Because these cells have preferential expression of CXCR3, we investigated whether CXCR3 was required for host defense activity against PC. Mice deficient in CXCR3 but CD4+ T cell intact, showed an initial delay but were able to clear the infectious challenge, indicating that CXCR3 signaling is not essential for clearance of PC. CD4-depleted mice had lower levels of monokine induced by IFN-γ, IFN protein-10 (IP-10), and IFN-inducible T cell α-chemoattractant at day 7 of infection and are permissive to PC infection. Overexpression of IP-10 in the lungs by adenoviral gene transfer did not accelerate clearance of infection in control mice but accelerated clearance by day 28 in mice depleted of CD4+ T cells. This effect was associated with increased recruitment of CD8+ T to the lungs with higher CXCR3+ expression levels and enhanced IFN-γ secretion upon in vitro activation compared with control mice. These results indicate that the CXCR3 chemokines are part of the host defense response to PC, and that IP-10 can direct Tc1 CD8+ T cell recruitment to the lungs and contribute to host defense against PC even in the absence of CD4+ T cells.
AB - We have previously shown that Tc1 CD8+ T cells have in vitro and in vivo effector activity against Pneumocystis (PC) infection in mice. Because these cells have preferential expression of CXCR3, we investigated whether CXCR3 was required for host defense activity against PC. Mice deficient in CXCR3 but CD4+ T cell intact, showed an initial delay but were able to clear the infectious challenge, indicating that CXCR3 signaling is not essential for clearance of PC. CD4-depleted mice had lower levels of monokine induced by IFN-γ, IFN protein-10 (IP-10), and IFN-inducible T cell α-chemoattractant at day 7 of infection and are permissive to PC infection. Overexpression of IP-10 in the lungs by adenoviral gene transfer did not accelerate clearance of infection in control mice but accelerated clearance by day 28 in mice depleted of CD4+ T cells. This effect was associated with increased recruitment of CD8+ T to the lungs with higher CXCR3+ expression levels and enhanced IFN-γ secretion upon in vitro activation compared with control mice. These results indicate that the CXCR3 chemokines are part of the host defense response to PC, and that IP-10 can direct Tc1 CD8+ T cell recruitment to the lungs and contribute to host defense against PC even in the absence of CD4+ T cells.
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U2 - 10.4049/jimmunol.177.3.1846
DO - 10.4049/jimmunol.177.3.1846
M3 - Article
C2 - 16849496
AN - SCOPUS:33746215187
SN - 0022-1767
VL - 177
SP - 1846
EP - 1854
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -