Human Cord Blood Leukocyte Innate Immune Responses to Defense Collagens

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Abstract
The innate immune system provides critical protection during initial infections before the generation of an appropriate adaptive (antibody or T cell mediated) immune response. These early defense mechanisms may be particularly critical for neonates in whom the adaptive immune system is not fully operational. Pattern recognition molecules target potential pathogens for destruction by the innate immune system, and likely facilitate the initiation of a pathogen-specific immune response. Defense collagens, such as C1q, MBL and SPA, comprise a family of such proteins that, via specific interactions with phagocytic cells, play a role in this first line of defense. To begin to assess the importance of these innate defense mechanisms in neonates, cord blood plasma and leukocytes were isolated, and responses to these components of the innate defense system were assessed. C1q enhanced the phagocytosis of targets suboptimally opsonized with either IgG or complement components, and this enhancement of phagocytosis was blocked by anti-CD93/C1qRP MAb by 57% to 68%. Flow cytometric analysis demonstrated that neonatal monocytes and neutrophils expressed CD93/C1qRP similarly to adult cells, with several-fold greater expression on monocytes than on neutrophils and essentially no expression on lymphocytes. Superoxide production in response to multivalent C1q by neonatal neutrophils was also comparable to adult cells. We also confirm that C1q and MBL are present in neonate circulation. Thus, the data demonstrate that these recognition and effector mechanisms of the innate system are functional in the newborn and similar to that of adult cells.