Macrophages, CD4+ or CD8+ Cells Are Each Sufficient for Protection against Chlamydia pneumoniae Infection through their Ability to Secrete IFN-γ

Abstract

By using a T, B, or NK cell-deficient mouse strain (recombinase-activating gene (RAG)-1−/−/common cytokine receptor γ-chain (γCR)), and T and B cell and IFN-γ-deficient (RAG-1−/−/IFN-γ−/−) mice, we have studied the generation of immunity against infection by Chlamydia pneumoniae. We found that IFN-γ secreted by innate-cell populations protect against C. pneumoniae infection. However, NK cells were not needed for such IFN-γ-dependent innate immune protection. Inoculation of wild type, but not IFN-γ−/− bone marrow-derived macrophages protected RAG-1−/−/IFN-γ−/− mice against C. pneumoniae infection. In line, pulmonary macrophages from RAG-1−/− C. pneumoniae-infected mice expressed IFN-γ mRNA. Reconstitution of RAG-1−/−/γcR−/− or RAG-1−/−/IFN-γ−/− mice with CD4+ or CD8+ cells by i.v. transfer of FACS sorted wild type spleen cells (SC) increased resistance to C. pneumoniae infection. On the contrary, no protection was observed upon transfer of IFN-γ−/− CD4+ or IFN-γ−/− CD8+ SC. T cell-dependent protection against C. pneumoniae was weaker when IFN-γR−/− CD4+ or IFN-γR−/− CD8+ SC were inoculated into RAG-1−/−/IFN-γ−/− mice. Thus both nonlymphoid and T cell-derived IFN-γ can play a central and complementary role in protection against C. pneumoniae. IFN-γ secreted by nonlymphoid cells was not required for T cell-mediated protection against C. pneumoniae; however, IFN-γ regulated T cell protective functions.

STAT1 Regulates IFN-αβ- and IFN-γ-Dependent Control of Infection withChlamydia pneumoniaeby Nonhemopoietic Cells

“…with CD4 ϩ or CD8 ϩ cells and infected with C. pneumoniae 24 days after cell transfer. CD4 ϩ or CD8 ϩ cells are here the only source of IFN-␥, the secretion of which is necessary and sufficient for protection (28). Inoculation of either CD4 ϩ or CD8 ϩ WT spleen cells into RAG-1 Ϫ/Ϫ /IFN-␥ Ϫ/Ϫ mice had a dramatic effect on protection; C. pneumoniae levels in lungs 21 days after infection were 100-to 1000-fold lower in reconstituted animals compared with unreconstituted controls (Fig.…”

“…Positive selection of CD4 ϩ and CD8 ϩ spleen cells CD4 ϩ cell and CD8 ϩ cell suspensions were prepared from spleens as described previously (28). Briefly, spleen cell suspensions were obtained from uninfected WT or STAT1 Ϫ/Ϫ mice and filtered through a nylon-wool column, incubated with either FITC-labeled rat anti-mouse CD4 (clone L3T4) or PE-labeled rat anti-mouse CD8␣ (clone 53-6.7), and CD4 ϩ or CD8 ϩ cells were sorted by using a FACSVantage sorter (BD Biosciences).…”

Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: Implications for vaccines

“…We consider that the immune system has designed a delicate system aimed at effective operation of TLR recognition, conferring on DCs the ability to distinguish danger signals from innocuous stimuli (i.e., nonrandom) and induce T cell-mediated adaptive immune responses to these dangers. This mechanism represents a substantial difference from macrophages, which react to TLR ligands by mediating direct antimicrobial innate effector responses (30)(31)(32).…”

Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll-like receptor 4 expression on macrophages

“…The degree of contamination by other cells was minimal. Macrophage transfer was performed as described (22). Briefly, under ether anesthesia, peritoneal macrophages (1 ϫ 10 7 cells) stimulated with PBS or poly I:C (50 g͞ml) suspended in 100 l of pyrogen-free PBS were injected i.v.…”