CpG oligodeoxynucleotides promote the host protective response against infection with Cryptococcus neoformans through induction of interferon-gamma production by CD4(+) T cells

In the present study, we elucidated the effect of synthetic CpG-containing oligodeoxynucleotides (ODN) on pulmonary and disseminated infection caused by Cryptococcus neoformans. CDF-1 mice were inoculated intratracheally with a highly virulent strain of this pathogen, which resulted in massive bacterial growth in the lung, dissemination to the brain and death. Administration of CpG-ODN promoted the clearance of C. neoformans in the lungs, decreased their dissemination to brain and prolonged the survival of infected mice. These effects correlated well with the enhanced production of interleukin (IL)-12 and interferon (IFN)-γ and attenuated secretion of IL-4 in bronchoalveolar lavage fluids (BALF) and promoted development of Th1 cells, as indicated by the increased production of IFN-γ by paratracheal lymph node cells upon restimulation with cryptococcal antigens. The IFN-γ synthesis in BALF was inhibited by depletion of CD8(+) and CD4(+) T cells on days 7 and 14 after infection, respectively, but not by depletion of NK and γδ T cells. Consistent with these data, intracellular expression of IFN-γ was detected predominantly in CD8(+) and CD4(+) T cells in the lung on days 7 and 14, respectively. The protective effect of CpG-ODN, as shown by the prolonged survival, was completely and partially inhibited by depletion of CD4(+) or CD8(+) T cells, respectively, but not by depletion of other cells. Finally, TNF-α was markedly induced by CpG-ODN, and the protective effect of this agent was strongly inhibited by neutralizing anti-TNF-α MoAb. Our results indicate that CpG-ODN alters the Th1–Th2 cytokine balance and promotes host resistance against infection with C. neoformans

Host's innate immune response to fungal and bacterial agents in vitro: up-regulation of interleukin-15 gene expression resulting in enhanced natural killer cell activity

Natural killer (NK) cells play an important role in the first line of defence against viral infections. We have shown earlier that exposure of human peripheral blood mononuclear cells (PBMC) to viruses results in rapid up-regulation of NK cell activity via interleukin-15 (IL-15) induction, and that this mechanism curtails viral infection in vitro. By using Candida albicans, Escherichia coli and Staphylococcus aureus, we now show here that exposure of PBMC to fungi and bacteria also results in an immediate increase of NK cytotoxicity. Reverse transcriptase–polymerase chain reaction and Western blot analyses as well as the use of antibodies against different cytokines revealed that IL-15 induction played a predominant role in this NK activation. These results indicate that IL-15 is also involved in the innate immune response against fungal and bacterial agents

Controlling Parameters on Facies Geometries of the Bahamas, an Isolated Carbonate Platform Environment

The Bahamas are among the most extensively studied carbonate regions in the world, and a number of phenomena typical of calcareous environments have been first observed in the Bahamas. Early geological research in the Bahamas was undertaken by Nelson (1853B) who surveyed their geography and topography. He noticed the “remarkable lowness of profile” and the dynamics of construction and destruction of the islands, outlined the biota and lithologies, described the formation of the carbonate rocks, and noticed the eolian origin of many Bahamian islands. Forty years later, the examination of modern carbonate environments rapidly progressed with the expedition of L. and A. Agassiz in 1893 (Agassiz 1894). Their explorations focused mainly on the fringing reefs of GE Great Bahama Bank. Research on abiotic carbonate components followed, by Vaughan (1914) who emphasized that carbonate constituents can originate from both skeletal secretion and chemical precipitation, and introduced the terms “organic” and “inorganic” limestones. Black (1933) first characterized the sedimentary facies on Great Bahama Bank and noted the significance of the widespread aragonitic mud. The sand-sized calcareous components of the Bahamas and their origin, including ooid sands, were described in detail in the classic papers by Illing (1954) and Newell et al. (1960)