Chronic inflammation and granuloma formation are associated with mononuclear cell infiltrates and are characteristic pathologic responses in tuberculosis. To identify host cell genes involved in tuberculous pathology, we screened macrophage cDNA libraries for genes induced by mycobacterial infection. One gene isolated in this screen, osteopontin (also known as early T lymphocyte activation protein 1 or Eta-1), was of particular interest because it is a cytokine and macrophage chemoattractant. Further study revealed that Mycobacterium tuberculosis infection of primary human alveolar macrophages causes a substantial increase in osteopontin gene expression. Osteopontin protein was identified by immunohistochemistry in macrophages, lymphocytes, and the extracellular matrix of pathologic tissue sections of patients with tuberculosis. Increased osteopontin expression also was found to be associated with silicosis, another granulomatous disease. The association of osteopontin with granulomatous pathology, together with the known properties of the protein, suggest that osteopontin may participate in granuloma formation. The strategy of identifying host genes whose expression is altered by infection thus can provide valuable clues to disease mechanisms and will be increasingly valuable as additional human genome sequences become available.Mycobacterial infections are among the most numerous in the world, with Mycobacterium tuberculosis believed to have infected one-third of the world's population (1). Aggravating the worldwide pandemic have been the emergence of resistant organisms and the concurrent HIV epidemic. These events have renewed interest in understanding the fundamental biology of the interactions between pathogenic mycobacteria and their host.Exposure to M. tuberculosis can lead to a pulmonary infection characterized by macrophage recruitment to the site of infection, followed in many cases by granuloma formation (2-4). M. tuberculosis is a facultative intracellular pathogen whose cellular habitat is the macrophage (5-9). Thus, the M. tuberculosis-macrophage relationship is of considerable interest. Previous investigations have revealed that interleukin 1, tumor necrosis factor-␣, interleukin 6, transforming growth factor-␤, and interleukin 8 production by macrophages is increased by exposure to mycobacteria (10)(11)(12)(13)(14). Negative effects of mycobacteria on macrophage antigen presentation (15) and responsiveness to cytokines (16, 17) also have been documented. However, little is known about the molecular mechanisms involved in granuloma formation.To gain insight into the host response to tuberculosis, we used differential screening of cDNA libraries to compare mRNAs of infected and uninfected macrophages. We reasoned that the identification of macrophage genes whose expression is altered after phagocytosis of M. tuberculosis might provide clues to pathogenesis. Using a model system that used a macrophage cell line (18, 19), we surveyed the population of macrophage mRNAs for those altered by my...

We created a cDNA library from feeding, female Ixodes scapularis ticks and screened the library with a subtracted probe to eliminate most genes common to feeding female and mating male I. scapularis ticks. Four unique genes were identified in this screen. One gene, Is 9, (represented by 16 cDNAs) was more highly expressed in female ticks. This gene encodes a putative glycine-rich protein, which matched a number of glycine-rich proteins including attachment cement proteins from Rhipicephalus appendiculatus. A second gene, Is 10 (represented by one cDNA) was also more highly expressed in female ticks, but did not match any other sequences in the GenBank database. The third gene, Is 11 (represented by one cDNA) was very similar to Drosophila sp. hsp68 and hsp70 genes and was expressed about equally in male and female ticks. The fourth gene, Is 12 (represented by two cDNAs) was also about equally expressed in male and female ticks, and was similar to a salivary gland gene from Ixodes ricinis. This gene also showed limited similarity to some cuticle genes from insects.