What does the term “maternal immunology” mean to you? As a mammal yourself, you probably consider things like microbial colonization during live birth, or the transfer of maternal antibodies through breast milk during the beginning of your life. But when you (or your pets or perhaps the animals you study) were born, you already had a head start on developing your own immune system, given the relatively long gestation period inside your mother. Animals that reproduce in this fashion are said to have “precocial young”, and are categorized as eutherians or “placental mammals”. However, not all mammals are alike: the marsupials – a.k.a your favourite koala, opossum or kangaroo at the zoo – reproduce entirely differently than “conventional” mammals, providing interesting implications for the evolution of maternal and juvenile immunology.
Marsupials gestate for very short periods of time and give birth to “altricial young”— newborns enter the world in a helpless condition requiring prolonged parental care. They complete most of their development outside of the womb in a pouch known as the marsupium or permanently attached to the mother’s teat. Thus, the development of marsupial immune systems occurs almost exclusively after birth. As such, marsupial young rely much more heavily on immune protection provided by the mother compared to eutherians. Here we review some of the findings in this growing field of immunology.
After birth, marsupial offspring (joeys) climb their way into their mother’s pouch, where they continue to develop for several months. Fittingly, marsupials have evolved multiple strategies to protect the young from harmful bacteria in the pouch.
When the pouch is empty, it contains abundant bacterial diversity, but as the birth of the young approaches, the mother begins grooming her pouch to combat bad bacterial colonizers. Key to this is the extraordinary expansion and diversification of antimicrobial peptide families encoded in the marsupial gemone, whose gene products are found in the mother’s saliva or in direct secretions into the pouch. After birth, the mother continues to groom both the pouch and the joey to keep bacterial besiegers at bay. The composition of any maternal commensal populations that may colonize the young is not yet well-understood.
Next comes a sophisticated lactation system, categorized by distinct changes in milk composition in order to meet the different nutritional and immunological requirements of the developing joey. The mother’s milk contains immunoglobulins and additional bactericidal compounds to combat pathogens. Immune cells such as neutrophils and macrophages are also transferred in milk, acting to neutralize any dangers that slip through the chemical defenses.
The protection provided via the mother’s milk is especially rich during the colostral phase, just after birth, to give the young a boost in protection at their most vulnerable stage. Certain possum species also provide a second immune boost just before the young exit the pouch. In sum, extensive and complex protection is maternally provided to altricial young, ensuring a safe environment for the joey to develop primary and secondary lymphoid tissues postnatally.
HEMATOPOIESIS IN THE JOEY
Newborn marsupials are essentially born without an adaptive immune system. However, lymphoid tissues begin to develop rapidly during postnatal life and eventually provide the young with immune independence.
Surprisingly, in contrast to eutherian newborns, marsupials are born with solid cartilaginous bones that leave no room for marrow, and thus do not provide a hematopoietic niche. Over the first month of development, the structure of the bones begins reorganizing and bone marrow fills the insides. Therefore, until the bone marrow (and later the thymus) is fully developed, early hematopoiesis occurs in the liver and spleen.
After birth, hematopoietic activity in the liver of newborns increases dramatically; it peaks during the first week of life in the pouch and then begins to decline. Concurrent with the decline of activity in the liver, hematopoiesis in the spleen increases. Initially, red pulp dominates with islands of erythroblast and myelocyte development. White pulp, the areas rich in lymphocytes, does not form until the bone marrow and thymus have completed development later in life.
The thymi of marsupials fully develop between 20 and 100 days post birth, depending on the species, and are structurally similar to eutherian thymi. However, not all marsupial species have the same number of thymi. Polyprotodonts — a largely carnivorous or insectivorous group of marsupials — have only one thoracic thymus, whereas most of the nearly exclusively herbivorous diprotodont species have an additional cervical thymus.
The reason for having two thymi is not well understood, although it has been hypothesized that a thymus in the neck region allows for more rapid growth and expansion than is possible when confined to the thorax. Excess thymic tissues may also provide additional cytokines and secretions needed to develop a sustained immunological competence in the altricial young. Indeed, within 2 to 3 months of postnatal development, the thymus of most species is fully mature. By this time, peripheral lymphoid organs such as lymph nodes, spleen and gut-associated lymphoid tissues begin to develop.
As the field of marsupial immunology moves forward, the aim will be to better characterize fully developed adult immune systems. The identification of highly divergent immune genes and unique maternal determinants has already laid to rest the idea that marsupial immune systems are inferior to those of eutherians. Overall, the exploration of marsupial lineages provides intriguing insights to the mechanisms of maternal immune transfer and the evolution of early immune development.
- Borthwick CR, Young LJ, Old JM. The Development of the Immune Tissues in Marsupial Pouch Young. Journal of Morphology 2014; 275(7):822-839.
- Deakin JE. Marsupial Genome Sequences: Providing Insight into Evolution and Disease. Scientifica 2012; 2012: 22pgs. Article ID: 543176.
- Edwards MJ, Hinds LA, Deane EM, Deakin JE. A Review of Complementary Mechanisms which Protect the Developing Marsupial Pouch Young. Developmental and Comparative Immunology 2012; 37 (2) 213- 220.
Heather MacGregor and Catherine Schrankel
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