Mike Criscitiello

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Verified

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• PhD
• Professor at Texas A&M University

OBJECTIVE Design and evaluate immune responses of neonatal foals to a mRNA vaccine expressing the virulence-associated protein A (VapA) of Rhodococcus equi . ANIMALS Cultured primary equine respiratory tract cells; Serum, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from 30 healthy Quarter Horse foals. METHO...

Comparative animal models generate fundamental scientific knowledge of immune responses. However, these studies typically are conducted in mammals because of their biochemical and physiological similarity to humans. Presently, there has been an interest in using teleost fish models to study intestinal immunology, particularly intestinal mucosa immu...

The genomes of most vertebrates contain many V, D, and J gene segments within their Ig loci to construct highly variable CDR3 sequences through combinatorial diversity. This nucleotide variability translates into an antibody population containing extensive paratope diversity. Cattle have relatively few functional VDJ gene segments, requiring innova...

In the mammalian immune system, the surrogate light chain (SLC) shapes the antibody repertoire during B cell development by serving as a checkpoint for production of functional heavy chains (HC). Structural studies indicate that tail regions of VpreB contact and cover the third complementarity-determining region of the HC (CDR H3). However, some sp...

The low diversity in marine mammal major histocompatibility complex (MHC) appears to support the hypothesis of reduced pathogen selective pressure in aquatic systems compared to terrestrial environments. However, the lack of characterization of the aquatic and evolutionarily distant Sirenia precludes drawing more generalized conclusions. Therefore,...

Cattle has a restricted repository of immunoglobulin heavy chain gene segments with only one family of V, 4 J and 16 D segments functional. Among these segments are a V and D that, together, encode a heavy chain with an ultralong CDR3 region which manifests as a “stalk” supporting a “knob” domain of which only the knob has antigen binding capabilit...

Amazonian (Trichechus inunguis) and West Indian (Trichechus manatus) manatees are aquatic mammals vulnerable to extinction found in the Amazon basin and the coastal western Atlantic. Toll-like receptors (TLR) play a key role in recognizing pathogen-associated molecular patterns using leucine-rich repeats (LRRs). We described the diversity of TLR4 a...

Natural killer (NK) cells play major roles in innate immunity against viruses and cancer. Natural killer receptors (NKR) expressed by NK cells recognize foreign- or self-ligands on infected and transformed cells as well as healthy cells. NKR genes are the most rapidly evolving loci in vertebrates, and it is generally difficult to detect orthologues...

Immunoglobulins and T cell receptors (TCR) have obvious structural similarities as well as similar immunogenetic diversification and selection mechanisms. Nevertheless, the two receptor systems and the loci that encode them are distinct in humans and classical murine models, and the gene segments comprising each repertoire are mutually exclusive. A...

Peptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which cause post-translational deimination, leading to structural and functional changes in target proteins. Deimination causes neo-epitope generation, affects gene regulation and also allows for protein moonlighting in health and disease. PADs are also a ph...

High allelic polymorphism and association with disease susceptibility has made the genes encoding major histocompatibility complex (MHC) antigen presentation molecules in humans, domesticated animals, and wildlife species of wide interest to ecologists, evolutionary biologists, and health specialists. The often multifaceted polygenism and extreme p...

Lysozymes play a key role in innate immune response to bacterial pathogens, catalyzing the hydrolysis of the peptidoglycan layer of bacterial cell walls. In this study, the genes encoding the c-type (TmLyzc) and g-type (TmLyzg) lysozymes from Totoaba macdonaldi were cloned and characterized. The cDNA sequences of TmLyzg and TmLyzc were 582 and 432...

In addition to canonical T and B cell receptors, cartilaginous fish assemble non‐canonical T cell receptors (TCR) that employ various B cell components. For example, shark T cells associate alpha (TCR‐alpha) or delta (TCR‐delta) constant (C) regions with immunoglobulin (Ig) heavy chain (H) variable (V) segments or TCR‐associated Ig‐like V (TAILV) s...

Synthetic molecules that mimic the function of natural enzymes or molecules have untapped potential for use in the next generation of drugs. Cyclic compounds that contain aromatic rings are macrocyclic cyclophanes, and when they coordinate iron ions are of particular interest due to their antioxidant and biomimetic properties. However, little is kn...

The bovine immune system is known for its unusual traits relating to immunoglobulin and antiviral responses. Peptidylarginine deiminases (PADs) are phylogenetically conserved enzymes that cause post-translational deimination, contributing to protein moonlighting in health and disease. PADs also regulate extracellular vesicle (EV) release, forming a...

Alligators are crocodilians and among few species that endured the Cretaceous–Paleogene extinction event. With long life spans, low metabolic rates, unusual immunological characteristics, including strong antibacterial and antiviral ability, and cancer resistance, crocodilians may hold information for molecular pathways underlying such physiologica...

Ab diversity in most vertebrates results from the assortment of amino acid side chains on CDR loops formed through V(D)J recombination. Cows (Bos taurus) have a low combinatorial diversity potential because of a small number of highly homologous V, D, and J gene segments. Despite this, a subset of the Ab repertoire (∼10%) contains exceptionally lon...

The loci encoding B and T cell Ag receptors are generally distinct in commonly studied mammals, with each receptor's gene segments limited to intralocus, cis chromosomal rearrangements. The nurse shark (Ginglymostoma cirratum) represents the oldest vertebrate class, the cartilaginous fish, with adaptive immunity provided via Ig and TCR lineages, an...

Peptidylarginine deiminases (PADs) are phylogenetically conserved calcium-dependent enzymes which post-translationally convert arginine into citrulline in target proteins in an irreversible manner, causing functional and structural changes in target proteins. Protein deimination causes generation of neo-epitopes, affects gene regulation and also al...

The evolutionary origins of CD1d molecules and the T cell receptors (TCR) that recognize them currently remain unknown. CD1d molecules control the functions of a specialized subset of lymphocytes called semi-invariant natural killer T (type I NKT) cells. Type I NKT cells recognize both the self and non-self agonist —α-galactosylceramide (αGC) and r...

Many γδ T cells typically bind antigen in a manner similar to that of immunoglobulins, recognizing and directly binding small molecules and intact proteins without presentation by classical MHC:Ag complexes. In this way, γδ T cells combine an innate-like immune response with an adaptive recognition strategy, providing both an immediate response to...

There is an ever-evolving need in the field of in vitro toxicology to improve the quality of experimental design, ie, from ill-defined cell cultures to well-characterized cytotoxicological models. This evolution is especially important as environmental health scientists begin to rely more heavily on cell culture models in pulmonary toxicology studi...

In mammals, haptoglobin (Hp) is an acute-phase plasma protein that binds with high affinity to hemoglobin (Hb) released by intravascular hemolysis. The resultant Hp-Hb complexes are bound and cleared by the scavenger receptor CD163, limiting Hb-induced oxidative damage. In this study, we show that Hp is a divergent member of the complement-initiati...

Problem Recently characterized interferon epsilon (IFNe) protects against sexually transmitted infections, including genital herpes simplex virus (HSV), in animal models. There are no reports of IFNe in genital tract secretions of pregnant women, and data on IFNe in non‐pregnant women are limited. This pilot study is the first to measure concentrat...

In jawed vertebrates from sharks to mammals, the thymus is the primary (or central) lymphoid tissue where T cells develop and mature. The particular stromal cell types, cytokine environment, and tissue organization in the thymus are essential for V(D)J recombination, positive selection for major histocompatibility complex recognition, and negative...

In mammals and probably all vertebrates, receptor editing of TCR alpha genes enhances immature T cell positive selection over a three-day interval in the thymic cortex. Surprisingly we found extensive somatic hypermutation (SHM) operating at the TCRα locus in the nurse shark thymus, implying that SHM contributes to receptor modifications that enhan...

Manatees are a vulnerable, charismatic sentinel species from the evolutionarily divergent order Afrotheria. We have previously described the immunoglobulin heavy chain locus of the Florida manatee (Trichechus manatus latirostris) and found limited antigen receptor diversity in this humoral arm of the adaptive immune system. We therefore investigate...

Since the discovery of the T cell receptor (TcR), immunologists have assigned somatic hypermutation (SHM) as a mechanism employed solely by B cells to diversify their antigen receptors. Remarkably, we found SHM acting in the thymus on α chain locus of shark TcR. SHM in developing shark T cells likely is catalyzed by activation-induced cytidine deam...

Frequency of mutation in TcR alpha V framework and complementarity determining regions for all mutation, nonsynonymous (NSYN) mutation only, or synonymous (SYN) mutation only.

CDR3 regions diversified by exonuclease activity and addition of N and P nucleotides. Alignment of nucleotides belonging to the join between variable (V) and joining (J) segments within TcRα thymocyte clones. We determined the putative ends of each V segment and putative beginning of each J segment by comparing alignments between different sharks,...

Tab-delimited text file containing sequences used in this paper for analysis of somatic hypermutation of TcR alpha chain.

The Florida manatee (Trichechus manatus latirostris) has limited diversity in the immunoglobulin heavy chain. We therefore investigated the antigen receptor loci of the other arm of the adaptive immune system: the T cell receptor. Manatees are the first species from Afrotheria, a basal eutherian superorder, to have an in-depth characterization of a...

New de novo transcriptome assembly and annotation methods provide an incredible opportunity to study the transcriptome of organisms that lack an assembled and annotated genome. There are currently a number of de novo transcriptome assembly methods, but it has been difficult to evaluate the quality of these assemblies. In order to assess the quality...

Antibodies are the key circulating molecules that have evolved to fight infection by the adaptive immune system of vertebrates. Typical antibodies of most species contain six complementarity-determining regions (CDRs), where the third CDR of the heavy chain (CDR H3) has the greatest diversity and often makes the most significant contact with antige...

Two populations of dendritic cells (DCs) are found in mammals, one derived from hematopoietic precursors (conventional/cDC), and another derived from mesenchymal precursors, the follicular DC (FDC); the latter is specialized for antigen presentation to B cells, and has only been definitively demonstrated in mammals. Both cDC and FDC are necessary f...

The antibody repertoire of Bos taurus is characterized by a subset of variable heavy (VH) chain regions with ultralong third complementarity determining regions (CDR3) which, compared to other species, can provide a potent response to challenging antigens like HIV env. These unusual CDR3 can range to over seventy highly diverse amino acids in lengt...

No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens (BG505 SOSIP) that antigenically mimic the HIV envelope glycoprotein (Env)¹ have improved the elicitation of potent isolate-specific antibody responses in rabbits² and macaques³, but so far failed to ind...

Manatees are a vulnerable, charismatic sentinel species from the evolutionarily divergent Afrotheria. Manatee health and resistance to infectious disease is of great concern to conservation groups, but little is known about their immune system. To develop manatee-specific tools for monitoring health, we first must have a general knowledge of how th...

The B cell receptor and secreted antibody are at the nexus of humoral adaptive immunity. In this review, we summarize what is known of the immunoglobulin genes of jawed cartilaginous and bony fishes. We focus on what has been learned from genomic or cDNA sequence data, but where appropriate draw upon protein, immunization, affinity and structural s...

In testing the hypothesis that all jawed vertebrate classes employ immunoglobulin heavy chain V (IgHV) gene segments in their T cell receptor (TCR)δ encoding loci, we found that some basic characterization was required of zebrafish TCRδ. We began by annotating and characterizing the TCRα/δ locus of Danio rerio based on the most recent genome assemb...

Model organisms such as Danio rerio are used to explore and model physiological reactions to stress, illness, and disease. Immune response is measured by quantifying lymphocyte presence and the production of mRNA encoding different immunoglobulin proteins. Because the method through which D. rerio is exposed to an antigen affects its immune respons...

Adipose tissue resident B cells account for more than 20% of stromal cells within visceral adipose tissues; however, their functions in the adipose tissue niche are poorly elucidated. Here we report that miR-150 modulates adipose tissue function by controlling activation of B cells and their interactions with other immune cells. miR-150KO mice disp...

Distinct methods are required for inducing mucosal versus systemic immunity in mammals for vaccine protection at the tissues most commonly breached by pathogens. Understanding of mucosal immunization in teleost fish is needed to combat aquaculture disease, understand emerging ecological threats, and know how vertebrate adaptive immunity evolved. He...

The antibody repertoire is the fundamental unit that enables development of antigen specific adaptive immune responses against pathogens. Different species have developed diverse genetic and structural strategies to create their respective antibody repertoires. Here we review the shark, chicken, camel, and cow repertoires as unique examples of stru...

The completion of the genome draft of the Florida manatee (Trichechus manatus latirostris) in 2012 made immunogenetic exploration of the Sirenia order more feasible. The endangered manatees are sentinel species for coastal ecosystems and their evolutionary origins are complex. It is believed that they evolved from a wading terrestrial mammal that b...

Transcriptome assembly techniques provide a valuable opportunity to learn more about non-model organisms. We present transcriptome assemblies for Pacific whiteleg shrimp (Litopenaeus vannamei), a species of great importance in global mariculture, that lacks solid transcriptome and genome references. We examine the new Pacific whiteleg transcriptome...

We present a new transcriptome assembly of the Pacific whiteleg shrimp (Litopenaeus vannamei), the species most farmed for human consumption. Its functional annotation, a substantial improvement over previous ones, is provided freely. RNA-Seq with Illumina HiSeq technology was used to analyze samples extracted from shrimp abdominal muscle, hepatopa...

Introduction: Sharks have successfully lived in marine ecosystems, often atop food chains as apex predators, for nearly one and a half billion years. Throughout this period they have benefitted from an immune system with the same fundamental components found in terrestrial vertebrates like man. Additionally, sharks have some rather extraordinary i...

It is well documented that various particulate matter — either incidental or engineered — are known to generate reactive oxygen species (ROS) in living cells. In circumstances where these reactive species are generated, antioxidant production is often increased. This balance in the biological reduction/oxidation (a.k.a. redox) state within the cell...

Based on a recent RNAseq transcriptome, we have surveyed the amino acid deduced sequences for potential antiviral targets. Our research program is focused on nucleotide metabolism that is required for synthesis of the DNA-double stranded circular white spot syndrome virus. Previous availavility of ESTs allowed us to get partial sequences by tblastn...

Arginine kinase (AK) is a key enzyme for energetic balance in invertebrates. Although AK is a well-studied system that provides fast energy to invertebrates using the phosphagen phospho-arginine, the structural details on the AK-arginine binary complex interaction remain unclear. Herein, we determined two crystal structures of the Pacific whiteleg...

Some species mount a robust antibody response despite having limited genome-encoded combinatorial diversity potential. Cows are unusual in having exceptionally long CDR H3 loops and few V regions, but the mechanism for creating diversity is not understood. Deep sequencing reveals that ultralong CDR H3s contain a remarkable complexity of cysteines,...

Many studies address the influence of the gut microbiome on the immune system, but few dissect the effect of T cells on gut microbiota and mucosal responses. We have employed larval thymectomy in Xenopus to study the gut microbiota with and without the influence of T lymphocytes. Pyrosequencing of 16S ribosomal RNA genes was used to assess the rela...

The B7 family of genes is essential in the regulation of the adaptive immune system. Most B7 family members contain both variable (V)- and constant (C)-type domains of the immunoglobulin superfamily (IgSF). Through in silico screening of the Xenopus genome and subsequent phylogenetic analysis, we found novel genes belonging to the B7 family, one of...

The invariant chain (Ii) is the critical third chain required for the MHC class II heterodimer to be properly guided through the cell, loaded with peptide, and expressed on the surface of antigen presenting cells. Here, we report the isolation of the nurse shark Ii gene, and the comparative analysis of Ii splice variants, expression, genomic organi...

There are many efforts in understanding the effects of nanoparticles on cell viability and metabolism, however, not much is known regarding the distinct molecular mechanisms of inflammation and cellular stress using low dosing concentrations. To address this gap in the literature, we utilized a novel experimental design that specifically probes the...

The frog Xenopus laevis is a model species for developmental biology but is also of significant interest to comparative immunologists. Amphibians are the oldest group of organisms in which both the B lymphocytes of some species undergo immunoglobulin (Ig) class switch recombination and also have a dedicated mucosal Ig isotype. The purpose of this s...

The immunological effects of quantum dots are dependent on a variety of factors including, but not limited to, exposure time and dosing concentrations. In this study, we investigated the influence of 15 nm CdSe/ZnS-COOH quantum dot nanocrystals (QDs) on cell density, viability, and morphology in human epidermal keratinocytes (HEK) and human dermal...

Chemokines and their receptors have been studied in several solid tumor models as mediators of inflammation. In turn, inflammation has been implicated in the promotion and progression of tumors, and as such, chemokines have been proposed as novel molecular targets for chemotherapy. While the expression of these molecules has been described in tumor...

When released from damaged erythrocytes free heme not only provides a source of iron for invading bacteria but also highly toxic due to its ability to catalyze free radical formation. Hemopexin (Hx) binds free heme with very high-affinity and thus protects against heme toxicity, sequesters heme from pathogens, and helps conserve valuable iron. Hx i...

The content and organization of the Xenopus tropicalis TCRα/δ locus was determined. This locus is highly conserved among tetrapods, with the genes encoding the TCRδ chains embedded with those encoding TCRα. However, the frog TCRα/δ is unusual in that it contains V genes that appear indistinguishable from those in the IgH locus (VH). These V genes,...

Cartilaginous fish are the oldest animals that generate RAG-based Ag receptor diversity. We have analyzed the genes and expressed transcripts of the four TCR chains for the first time in a cartilaginous fish, the nurse shark (Ginglymostoma cirratum). Northern blotting found TCR mRNA expression predominantly in lymphoid and mucosal tissues. Southern...

Somatic hypermutation (SHM) is a mechanism B cells use while responding to antigen for affinity maturation, and is also employed in the diversification of the primary B cell repertoire in the gut associated lymphoid tissues of ruminants. Recently it was discovered that SHM operates at the T cell receptor γ locus of the sandbar shark. We have looked...

During T cell differentiation, medullary thymic epithelial cells (MTEC) expose developing T cells to tissue-specific antigens. MTEC expression of such self-antigens requires the transcription factor autoimmune regulator (Aire). In mammals, defects in aire result in multi-tissue, T cell-mediated autoimmunity. Because the T cell receptor repertoire i...

The discovery of a fourth immunoglobulin (Ig) light (L) chain isotype in sharks has revealed the origins and natural history of all vertebrate L chains. Phylogenetic comparisons have established orthology between this new shark L chain and the unique Xenopus L chain isotype sigma. More importantly, inclusion of this new L chain family in phylogenet...

We have characterized the genomic organization of the three zebrafish L chain isotypes and found they all differed from those reported in other teleost fishes. Two of the zebrafish L chain isotypes are encoded by two loci, each carrying multiple V gene segments. To understand the derivation of these L chain genes and their organizations, we perform...

Distinctive Ig and T cell receptor (TcR) chains define the two major lineages of vertebrate lymphocyte yet similarly recognize antigen with a single, membrane-distal variable (V) domain. Here we describe the first antigen receptor chain that employs two V domains, which are generated by separate VDJ gene rearrangement events. These molecules have s...