MATERNAL

IN TELEOST FISHES

Shyam K U & Nesnas E A

Maternal Immunity

Maternal immunity refers to the immunity transferred across the placenta, colostrum, milk or eggs from mother to offspring, which is supposed to play a key role to protect the vulnerable offspring against pathogenic attacks.

Maternal transfer of immunity is defined as the immunity transferred from mother to offspring, which is supposed to play a key role in protecting the vulnerable offspring against pathogenic attacks at early stages of life (Yue et al., 2013).

Maternal Immunity

These maternally-transferred factors include,

IgM

lysozymes

lectin

complement components

cathelicidin

yolk proteins - phosvitin and lipovitellin

1

5

2

4

6

3

LC

LC

CA

Y

Fish eggs are in most cases cleidoic, i.e. closed free-living system following fertilization.

They are therefore supposed to depend upon these maternal immunity for protection against invading pathogens before full maturation of immunological systems.

Both innate and adaptive type of immunity are transferred of from mother to offspring in fishes.

Mouth bearers can transfer some immunity to larvae through the mucus secreted from mouth cavity.

Delayed maturation of lymphoid organs and immuno-competence in fish.

The concept of maternal transfer of immunity is more than 100 years old

Maternally derived immunity is essential

Little or only limited ability of developing fish embryos and larvae to synthesize specific antibodies after certain

weeks of hatching.

Ig/antibody

Innate immunity

complement

factors

Tele

osts

serine protease

like molecules

Adaptive immunity

serum amyloid

A

a macroglobulin

other types of lectins

Transferred maternally by protein or mRNA in several fish species.

Transfer of maternally-derived immune factors

Previous studies on several fish species have shown that maternal IgM is able to be transferred from mother to offspring

Likewise, maternal transfer of the innate immune factors to offspring has also been reported in different teleost species.

Moreover, immunization of parents results in a significant increase in IgM levels and lysozyme activities in the eggs compared to control.

Vg-derived proteins Vg is an egg yolk precursor protein, present in the females of all

oviparous species including fish, amphibians, reptiles, birds, most invertebrates and the platypus.

Usually synthesized extraovarianly and transported by the circulation system to the ovary.

Where it is internalized into growing oocytes and proteolytically cleaved to generate yolk proteins, phosvitin (Pv) and lipovitellin (Lv).

These are later used as the nutrients by developing embryos.

Initially regarded as a female-specific protein.

However its synthesis, albeit in smaller quantities, has been shown to occur in male and sexually immature animals.

Vg may, in addition to being involved in yolk protein formation, play a role independent of gender.

Recently, Vg has been shown to be an immune-relevant molecule involved in the defense of host against the microbes including bacterium and virus.

Pv and Lv, that both are proteolytically cleaved products of Vg, are naturally transferred from mother to eggs in fish.

Traditionally considered as the yolk reserves of nutrients essential for growth and development.

Pv and Lv, may also play an immunological role in developing embryos and larvae.

Pv was proven to possess an antimicrobial activity in zebrafish embryos and larvae.

Chicken egg yolk Pv was also shown to be able to inhibit the growth of the Gram-negative bacterium Escherichia coli .

Fish native Lv was associated with the immune defense of rosy barb embryos and larvae.

Pv and Lv are maternally-transferred proteins involved in both nutritional supply and immune defense in embryos and larvae in fishes.

Complement components

Consists of 35 soluble and membrane proteins

Part of first line of defense mechanism

Contains components as C1, C2, C3, C4, C5, C6, C7, C8, C9, factor B, H, I, D, E

Activated by 3 pathways

ACP- triggered by the certain structures on microbial surface in an antibody-independent manner.

CCP - initiated by binding of antibody to the C1 complex.

MBLP - activated by binding of microbial polysaccharides to circulating lectins, such as mannose binding lectin (MBL).

Different complement components (C3, C4, C5, C6, C7, Bf & Df) have been demonstrated to be transmitted from mother to offspring in rainbow trout, carp, spotted wolf fish and Atlantic salmon.

First evidence is from the zebrafish embryo (C3 & Bf).

It is associated with the early defense against pathogens in developing embryos and larvae.

Maternal immunization caused a remarkable increase in C3 and Bf in the mother and a corresponding increase in the offspring.

The embryos derived from immunized D. rerio were significantly more tolerant to the pathogenic bacterium Aeromonas hydrophila than those from unimmunized mother.

Mode of action of maternally-derived immune factors

Maternally-transferred immunity can not only protect fish embryos and larvae but also prevent them from vertical transfer from mother to offspring.

Both Pv and Lv were able to bind to the microbial conserved components(PAMPs), including LPS (G – ve) PGN (G – ve and + ve ) and lipoteichoic acid (LTA) of G + ve bacteria.

Pv is an effector molecule capable of killing bacteria directly.

Lv is an opsonin capable of enhancing macrophage phagocytosis.

Immune factor Function

Lysozymes catalyze hydrolysis of 1,4-beta-linkages of bacterial cell walls,

thereby causing bacterial lysis

Lectins interact with pathogenic surface carbohydrates leading to

opsonization, phagocytosis or activation of complement

Cathelicidin an inhibitory effect on bacterial growth via degrading into

small peptides or stimulating the release of cytokines enabling a more effective response to invading pathogens

Immunoglobulins such as IgM opsonize bacteria, resulting in their degradation and

eradication by phagocytic cells.

Maternally-transferred complement components in fish eggs operate via the AP, protecting embryos and larvae against pathogenic attack.

Mode of maternally-derived immune factor transfer

Whole the mode of maternally-derived immune factor transfer remains largely unknown.

Mode of IgM and yolk protein transfer – reported in fish.

Maternal IgM is transferred from mother to offspring through yolk in birds, reptiles and fishes.

In oviparous fishes, maternal IgM is initially transferred via yolk to immature oocytes during vitellogenesis and then to eggs and yolk sac larvae in a sequential manner.

In viviparous fishes, IgM is secreted from the epithelia of the ovigerous lamellae of pregnant females into ovarian cavity fluid and absorbed by enterocytes of the hypertrophied hindgut in foetus.

Maternal IgM is transferred to piscine eggs by the transcytosis across follicle cells.

In the entire IgM transfer process, follicular cells probably play an active role because of the presence of IgM within thecal and granulosa cells (and in the interposed basement membrane) of pre-vitellogenic and vitellogenic follicles.

Maternal IgM can also be incorporated into fish oocytes together with Vg.

Autogenous IgM synthesis and/or transfer of IgM mRNA are also possible because a significant level of IgM gene transcription has been observed in teleost oocytes.

In case of teleosts, maternally derived IgM usually persists for limited duration, which gets exhausted within the completion of yolk absorption process and completely disappear during larval stages.

The persistence of maternal Ig - depending upon body size and metabolic rate.

Yolk proteins Transfer of Vg into piscine growing oocytes is dependent upon their

plasma membrane receptor for Vg.

Vg receptors have eight-repeat ligand-binding domain as key structural elements and these multiple ovarian Vg receptors are responsible for interaction with different types of Vg proteins.

It has been found that the lipovitellin domain of teleost Vg mediates its binding to the oocyte receptor.

Interestingly, Vg receptor can be recycled to the oocyte surface during the vitellogenic growth phase.

Age

Maturation

Reproduction

Factors affecting maternal immunity transfer

Water pollution

Adverse environmental

Conditions

Stress conditions like handling and

crowding

Transfer is particularly sensitive to the availability of specific nutrients or minerals that are required as materials or precursors for the synthetic process of immune factors.

Availability of nutrients such as protein, vitamins, fat and fatty acid all affects the growth, maturation, reproductive performances (including the process of vitellogenesis, fertilization and hatchability) and immunity of brood,

and then impairs embryonic development and larval health

The pathogenic environment experienced by brood fish during vitellogenesis affects the quality and quantity of the immune factors transferred to offspring.

Possible applications in fish culture

Maternal immunity can therefore be used as an alternative strategy to promote the immunity of fish larvae, thus increasing their survival rate.

Practically, this can be easily achieved by feeding brood fish with specific nutrients like vitamins or immunizing brood fish with vaccines like inactivated pathogens.

Famous findings….

The administration of 0.2% β-glucan to rainbow trout fry only instead of feeding both brood fish and fry could have the same positive effects in promoting the immunity of fry and resistance to Y. ruckeri (Ghaedi G et al., 2015).

Transfer of maternal immune factors from mother to offspring is particularly sensitive to the availability of specific nutrients or minerals that are needed as materials or precursors for the synthetic process of immune factors (Zhang et al., 2013).

The protein extracts of scallop eggs exhibited remarkable agglutination activity and bactericidal effect against gram-negative bacteria Escherichia coli and Vibro anguillarum, and fungi Pichia pastoris. The results indicated that scallop eggs or embryos received maternal derived immune competence to defense against the invading pathogens. (Yue F et al., 2013)

It therefore seems that a maternally transmitted disease resistance induced by glucan, protected the larvae against a WSSV infection. (Huang C-C et al., 1999)

The physiological condition of parents has a profound effect on their offspring fitness by providing non-genetic factors, such as hormones and nutrients (Groothuis et al., 2005; Vijendravarma et al., 2010).

The maternal transferred immunity from mother with immune experience has positive impact on the offspring immunity or disease resistance, which is termed as trans-generational immune priming (TGIP) (Sadd et al., 2005).

In invertebrate, trans-generational effect of immunity has been first demonstrated in shrimp Penaeus monodon that offspring derived from glucan-injected mothers have significantly higher survival rates than the control group against WSSV infection (Huang and Song 1999).

Conclusion Alternative strategy to promote the immunity of

fish larvae

Criteria for selective breeding programmes and/or large scale brood stock immunization programmes.

Further studies has to initiate to examine the degree of immunity transferred (species-wise) and relationship between egg size and the efficiency of maternal immunity.

References Zhang S, Wang Z, Wang H (2013). Review - Maternal immunity in fish,

Developmental and Comparative Immunology 39; 72–78 Ghaedi G, Keyvanshokooh S, Azarma H M, Akhlaghi M (2015). Effects of dietary β-

glucan on maternal immunity and fry quality of rainbow trout (Oncorhynchus mykiss), Aquaculture 441; 78–83

Huang C-C and Song Y-L (1999). Maternal transmission of immunity to white spot syndrome associated virus (WSSV) in shrimp (Penaeus monodon ), Dev. and Comp. Immunology 23; 545 – 552

Wang H, Ji D, Shao J, Zhang S (2012). Maternal transfer and protective role of antibodies in zebrafish Danio rerio, Molecular Immunology 51; 332– 336

Mulero I, García-Ayala A, Meseguer J, Mulero V (2007). Maternal transfer of immunity and ontogeny of autologous immunocompetence of fish: A minireview, Aquaculture 268; 244–250

Swain P. and Nayak S.K. (2009). Review - Role of maternally derived immunity in fish, Fish & Shellfish Immunology 27; 89–99

Mingming H, FuHong D, Zhen M, Jilin L (2014). The effect of vaccinating turbot broodstocks on the maternal immunity transfer to offspring immunity, Fish & Shellfish Immunology 39; 118-124