Inefficiency of C3H/HeN Mice to Control Chlamydial Lung Infection Correlates with Downregulation of Neutrophil Activation during the Late Stage of Infection

We previously reported that massive infiltration of neutrophils in C3H/HeN （C3H） mice could not efficiently control Chlamydia muridarum （Cm） infection and might contribute to the high susceptibility of these mice to lung infection. To further define the nature of neutrophil responses in C3H mice during chlamydial infection, we examine the expression of adhesion molecules and CDllb related to neutrophils infiltration and activation, respectively, following intranasal Cm infection. The results showed that the expression of selectins （E-selectin, P-selectin and L-selectin）, and intercellular cell adhesion molecule-1 （ICAM-1） in the lung of C3H mice increased more significantly than in C57BL/6 （B6） mice, the more resistant strain. These results correlated well with the massive neutrophils infiltration in C3H mice. In contrast, CDllb expression on peripheral blood and lung neutrophils in C3H mice exhibited a significant reduction compared with B6 mice during the late phage of infection （day 14）. These findings suggest that the high-level expression of adhesion molecules in C3H mice may enhance neutrophils recruitment to the lung, but the decline of CDllb expression on neutrophils may attenuate neutrophil function. Therefore, CDllb down-regulation on neutrophils may contribute to the failure of C3H mice to control chlamydial lung infection.

Type 1 T-cell responses in chlamydial lung infections are associated with local MIP-1a response

Chemokines and their receptors are important mediators of leukocyte trafficking and recruitment and sometimes work as modulators of T-cell responses during infections and inflammation.Modulating the biological activity of chemokines has been found to influence the course of diseases.However,little is known about the role of chemokine responses during chlamydial lung infections.We therefore analyzed the dynamics of multiple chemokines,which are frequently associated with type 1(Th1)T cell immune responses,and their receptors for their expression in the lungs during Chlamydia muridarum(Cm)infections.We also examined the relationship between chemokine responses and the development of Th1 responses as well as the clearance of infection.Our results showed that in parallel with the high levels of gamma interferon(IFN-c)and IL-12 production in the lungs and draining lymph nodes,and the expansion of IFN-c-producing CD4 and CD81 T cells,the production of the cell-related chemokines RANTES,IFN-c-inducible protein-10(IP-10)and macrophage inflammatory protein-1a(MIP-1a)and their receptor CCR1 was elevated in the lung tissues after infection.Interestingly,in a later phase of infection,the expression of RANTES and IP-10 remained elevated but the expression of MIP-1a and CCR1 decreased to a low level,which suggests a closer association with the pattern of Th1 cytokine responses in the process of infection.These results suggest a close association between the MIP-1a response and the Th1-type T-cell responses in chlamydial lung infections .