Macrophages orchestrate innate immunity by phagocytosing pathogens and coordinating inflammatory responses 1 . Effective defence requires the host to discriminate between different pathogens. The specificity of innate immune recognition in Drosophila is mediated by the Toll family of receptors 2,3 ; Toll mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial defence 4-6 . A large number of Toll homologues have been identified in mammals, and Toll-like receptor 4 is critical in responses to Gram-negative bacteria 7-11 . Here we show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes containing yeast, and that a point mutation in the receptor abrogates inflammatory responses to yeast and Gram-positive bacteria, but not to Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes of innate immune receptors cooperate to mediate host defence: phagocytic receptors, such as the mannose receptor, signal particle internalization, and the Toll-like receptors sample the contents of the vacuole and trigger an inflammatory response appropriate to defence against the specific organism.
Macrophages orchestrate innate immunity by phagocytosing pathogens and coordinating inflammatory responses. Effective defence requires the host to discriminate between different pathogens. The specificity of innate immune recognition in Drosophila is mediated by the Toll family of receptors; Toll mediates anti-fungal responses, whereas 18-wheeler mediates anti-bacterial defence. A large number of Toll homologues have been identified in mammals, and Toll-like receptor 4 is critical in responses to Gram-negative bacteria. Here we show that Toll-like receptor 2 is recruited specifically to macrophage phagosomes containing yeast, and that a point mutation in the receptor abrogates inflammatory responses to yeast and Gram-positive bacteria, but not to Gram-negative bacteria. Thus, during the phagocytosis of pathogens, two classes of innate immune receptors cooperate to mediate host defence: phagocytic receptors, such as the mannose receptor, signal particle internalization, and the Toll-like receptors sample the contents of the vacuole and trigger an inflammatory response appropriate to defence against the specific organism.
Maternal cells have recently been found in the circulation and tissues of mothers' immune-competent children, including in adult life, and is referred to as maternal microchimerism (MMc). Whether MMc confers benefits during development or later in life or sometimes has adverse effects is unknown. Type 1 diabetes (T1D) is an autoimmune disease that primarily affects children and young adults. To identify and quantify MMc, we developed a panel of quantitative PCR assays targeting nontransmitted, nonshared maternal-specific HLA alleles. MMc was assayed in peripheral blood from 172 individuals, 94 with T1D, 54 unaffected siblings, and 24 unrelated healthy subjects. MMc levels, expressed as the genome equivalent per 100,000 proband cells, were significantly higher in T1D patients than unaffected siblings and healthy subjects. Medians and ranges, respectively, were 0.09 (0 -530), 0 (0 -153), and 0 (0 -7.9). Differences between groups were evident irrespective of HLA genotypes. However, for patients with the T1D-associated DQB1*0302-DRB1*04 haplotype, MMc was found more often when the haplotype was paternally (70%) rather than maternally transmitted (14%). In other studies, we looked for female islet  cells in four male pancreases from autopsies, one from a T1D patient, employing FISH for X and Y chromosomes with concomitant CD45 and  cell insulin staining. Female islet  cells (presumed maternal) formed 0.39 -0.96% of the total, whereas female hematopoietic cells were very rare. Thus, T1D patients have higher levels of MMc in their circulation than unaffected siblings and healthy individuals, and MMc contributes to islet  cells in a mother's progeny.quantitative PCR ͉ chimerism ͉ autoimmunity ͉ pancreas ͉ HLA
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