Monocytes: What are they? Importance and Function in Premature Fetuses and Neonates

They are the largest of all white blood cells and play an important role in the defense against germs and inflammation.

Importance

Monocytes and macrophages , which are classified among leukocytes, play a fundamental role in the innate immune system. Its origin is based on a common myeloid precursor, while both play an important role in innate immunity.

Macrophages, which are produced from monocytes after exposure to certain stimuli, circulate in the bloodstream; They are ephemeral because they experience spontaneous apoptosis.

However, in response to differentiation factors, some monocytes migrate and populate tissues, thus escaping their apoptotic fate and becoming macrophages that have a longer life and are found in almost all organs of the body.

Residing as phagocytic cells in lymphoid and non-lymphoid tissue, they have the ability to recognize a wide range of pathogens and are efficient phagocytes, while also inducing the production of inflammatory cytokines.

Monocytes have the potential to differentiate into dendritic cells (DCs) or tissue macrophages, although many CDs and tissue macrophages do not originate from monocytes in a stable state.

Under certain circumstances, monocytes differentiate in DC during infection that produce inflammatory mediators such as TNF-α, nitric oxide (NO-) and reactive oxygen species, as in infection with Listeria monocytogenes.

However, under other conditions, monocytes differentiate into mucosal macrophages with a different surface phenotype and capacity to produce inflammatory mediators, as in Toxoplasma infection.

Monocytes and their precursors can activate or inhibit the immune response, depending on the local and systemic signals and the pathogen involved.

Monocytes acquire the capacity for differentiation and the production of inflammatory mediators early in life. However, there is evidence of immaturity of the innate immune system in human fetuses, including its fundamental component, the phagocyte mononuclear system.

It is considered that this immaturity is functional in its origin, since the different types of cells involved in innate immunity are present in the fetus, although their immune “virtues” are questioned.

Newborns are prone to serious bacterial infections, and mortality caused by infections is high despite prompt antibiotic therapy: this phenomenon is especially common among preterm infants.

As the production of phagocytes and their proper functioning are crucial for an effective bactericidal immune mechanism, the malfunctioning of the mononuclear system may explain the vulnerability of infants to infections.

Function of monocytes in premature fetuses and neonates

Few studies on the immune system of the fetus and neonate are available and knowledge is lacking regarding the phagocytic and oxidative capacity of macrophages or their expression of adhesion molecules.

However, it has been determined that several functions of the inborn fetal immune system are essentially different from those observed in term infants or adults.

A significantly decreased phagocytic activity of fetal monocytes has been described, which is in sharp contrast to the high production of reactive oxygen products.

In addition, significant amounts of fetal monocytes are capable of producing proinflammatory cytokines in response to inflammatory stimulation.

However, a difference in the pattern of cytokine production was observed compared to that demonstrated in more mature individuals; in other words, there was a marked decrease in the number of IL-6 and positive monocytes for the tumor necrosis factor.

In contrast to the term infantile responses, the TNF-α and IL-6 responses of preterm infants with a gestational age (GA) of <30 weeks) were severely affected due to a decreased proportion of monocytes that produce cytokines

Similarly, responses between premature monocytes with respect to whole cord blood stimulated with live B-group Streptococcus (GBS) were almost invariably less robust than those seen in full-term infants.

In newborns, the expression of several adhesion molecules involved in the migration of monocytes has been compromised appreciably, which leads to a decrease in the neonatal immune response. In addition, qualitative deficiencies of phagocyte function in preterm infants have been demonstrated.

The fact that newborns, particularly those born prematurely, generate comparatively low amounts of G-CSF after inflammatory stimulation suggests that this may partly explain their upwardly deficient regulation of both neutrophil production and function during the infection.

Regarding the impact of prematurity on phagocytosis of monocytes, the data are very limited.

However, research on premature neutrophils and alveolar macrophages of premature infants has documented a reduction in bacterial absorption.

While other stimuli derived from bacteria have indicated that monocytes from premature infants have an intrinsic deficiency related to gestational age in their ability to recognize.