Allograft Inflammatory Factor-1 in Metazoans: Focus on Invertebrates

Abstract

Allograft inflammatory factor-1 (AIF-1) is a calcium-binding scaffold/adaptor protein often associated with inflammatory diseases. Originally cloned from active macrophages in humans and rats, this gene has also been identified in other vertebrates and in several invertebrate species. Among metazoans, AIF-1 protein sequences remain relatively highly conserved. Generally, the highest expression levels of AIF-1 are observed in immunocytes, suggesting that it plays a key role in immunity. In mammals, the expression of AIF-1 has been reported in different cell types such as activated macrophages, microglial cells, and dendritic cells. Its main immunomodulatory role during the inflammatory response has been highlighted. Among invertebrates, AIF-1 is involved in innate immunity, being in many cases upregulated in response to biotic and physical challenges. AIF-1 transcripts result ubiquitously expressed in all examined tissues from invertebrates, suggesting its participation in a variety of biological processes, but its role remains largely unknown. This review aims to present current knowledge on the role and modulation of AIF-1 and to highlight its function along the evolutionary scale.

Keywords: AIF-1; Iba1; bacterial challenge; immunity; inflammation; invertebrates; macrophages.

Figure 1

(A) Neighbor-joining (NJ) optimal tree based on selected metazoan allograft inflammatory factor-1 (AIF-1)-related proteins. The tree was generated using MEGA X including AIF-1 from different species ranging from mammals to porifera. The amino acid sequences of two choanoflagellates are also included in the tree. All the sequences used were obtained from GenBank at NCBI. The evolutionary history was inferred using the NJ method. The evolutionary distances were computed using the Poisson correction method and are in the units of the number of amino acid substitutions per site. Bootstrap test: 1000 replicates. All ambiguous positions were removed for each sequence pair. (B) Condensed tree of (A) showing relationships among taxa. Percent identity values (min-max values amongst those observed in each metazoan group) are indicated in parentheses. † indicates Homo sapiens AIF-1 reference identity value (100%).

Figure 2

Multiple alignment among the sequences analyzed in Figure 1 as obtained by Clustal Omega (default parameters). EF-hand, calcium-binding motifs (Efh) are highlighted in grey. Asterisks (*) correspond to single, fully conserved residues. Colons (:) indicate conservation of residues sharing strongly similar properties (equivalent to scoring > 0.5 in the Gonnet PAM 250 matrix). Periods (.) indicate conservation of residues with weakly similar properties (equivalent to scoring ≤ 0.5 and > 0 in the Gonnet PAM 250 matrix).