Host-microbe signaling during microbial invasion and host phagocytosis. Host-microbe signaling during microbial invasion and host phagocytosis. Animal innate immunity acts to detect and manage microbial invaders, both negative and positive. Whatever the quality of the interaction, the host needs to recognize the presence of the microbe and then launch downstream effector pathways to either destroy negative invaders or foster the growth of mutualistic ones. There are many excellent reviews of host-microbe signaling that cover these events in great detail (173, 233, 377). For direct detection of microbes, hosts express a dizzying array of proteins, termed pattern recognition receptors (PRRs) (Table 1), either secreted or on cell surfaces that recognize signature microbial compounds termed microbe-associated molecular patterns (MAMPs). (PRRs depicted: C3R, complement 3 receptor; Nods, nucleotide-binding oligomerization domain proteins; SRs, scavenger receptors; TLRs, toll-like receptors). MAMPs are a variety of sugar, protein, lipid, and nucleic acid compounds that are essential to microbial survival and often unique to certain microbe groups. They include lipopolysaccharide (LPS), peptidoglycan (PG), glycans, and glycosylphosphatidylinositol (GPI) anchors. Host cells can also detect the presence of microbes indirectly through the process of opsonization that can amplify a host response. Invading microbes become coated with secreted host compounds or opsonins, such as complement protein (C3) or immunoglobulins (in the case of vertebrates). Like MAMPs, opsonins then bind PRRs on host cell surfaces. The binding of PRRs to MAMPs or opsonins starts a signaling cascade, often involving the activation of the master immunity regulator nuclear factor κB (NF-κB), which then launches a large array of host responses. In the case of invading pathogens, these responses can include phagocytosis of the microbe, an inflammatory response, antimicrobial killing mechanisms, and initiation of host cell apoptosis or autophagy. The three processes shown within the box are described in more detail in Appendix 1. Simon K. Davy et al. Microbiol. Mol. Biol. Rev. 2012; doi:10.1128/MMBR.05014-11