In conclusion, we found a very low prevalence of MBL deficiency in subjects who were at increased risk for experiencing AECOPDs and no association between MBL deficiency and time to first acute exacerbation, frequency of acute exacerbations, or percent of subjects requiring hospitalization for acute exacerbations in subjects with MBL deficiency regardless of how deficiency was defined. Accordingly, our data do not support the idea that MBL might be a therapeutic target to reduce the incidence of AECOPDs. Rather, they imply that, while COPD is an inflammatory disorder with systemic manifestations, the fundamental pathophysiology of COPD differs from conditions in which MBL deficiency seems to be a clear risk factor (ie, childhood pneumonia, rheumatoid arthritis, systemic lupus). The changing phenotype of microglia from homeostasis to disease It has been nearly a century since the early description of microglia by Rio-Hortega; since then many more biological and pathological features of microglia have been recognized. Today, microglia are generally considered to be beneficial to homeostasis at the resting state through their abilities to survey the environment and phagocytose debris. However, when activated microglia assume diverse phenotypes ranging from fully inflamed, which involves the release of many pro-inflammatory cytokines, to alternatively activated, releasing anti-inflammatory cytokines or neurotrophins, the consequences to neurons can range from detrimental to supportive. Due to the different experimental sets and conditions, contradictory results have been obtained regarding the controversial question of whether microglia are “good” or “bad.” While it is well understood that the dual roles of activated microglia depend on specific situations, the underlying mechanisms have remained largely unclear, and the interpretation of certain findings related to diverse microglial phenotypes continues to be problematic. In this review we discuss the functions of microglia in neuronal survival and neurogenesis, the crosstalk between microglia and surrounding cells, and the potential factors that could influence the eventual manifestation of microglia. I. Introduction II. The origin of microglia III.Microlgia the dual natures of neurotoxicity and neuroprotection IV.Crosstalk between microglia and other brain cells 1. Cross talk between microglia and neurons: neurons as regulators of microglial activation 2. Cross talk between astrocytes and microglia: reciprocal influences 3. Microglia-T cell crosstalk:key determinants for the Introduction Microglia are generally considered the immune cells of the central nervous system (CNS) and account for 10% of the total glial cell population in the brain. In a normal physiological environment, they work as sentinel cells by continually screening the brain tissue; they actively participate in pathological processes by changing morphology, expressing various antigens and becoming phagocytic. During the past 20 years, thousands of papers have been published describing both the detrimental and beneficial roles of microglia in various brain disorders, from acute infection or stroke to the long and chronic process of neurodegeneration. Microglia have been firmly established as a key cellular component involved in the eventual outcome of inflammation and eventually contribute to the chronic neurodegeneration; The physiology and signaling of microglia have been comprehensively reviewed by Kettenmann's series papers [1] [2] [3] [4] [5] [6] , however, the regulation of microglial activity is a highly complex system, and the responses of microglia are tailored in a multi-factor dependent manner, and which are the focus we try to review in this paper.