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Health and Immunity

Posted July 17, 2025

Honey bees are constantly exposed to contact with many types of pathogens. However, during evolution they developed a number of immune mechanisms. At the individual level, they comprise 1) resistance mechanisms associated with anatomical and physiological barriers of the body, 2) cell-mediated immunity involving immune cells (hemocytes), 3a) congenital humoral (body fluid), and 3b) induced humoral resistance based on the action of antimicrobial peptides (AMPs). AMPs are small proteins that play a crucial role in the innate immune system, helping to defend against a wide range of microorganisms, including bacteria, fungi, and viruses. In addition to the individual resistance of each bee, there is also a defense mechanism activated at the colony level. Shared secretion resistance is connected with the presence of antipathogenic compounds in secretions and in bee products. Social immunity is associated with hygienic and nursing behaviors, as well as with age-based work activities in the colony, swarming (and the emergence of laying workers), and the changing behavior of sick individuals.

Innate and Adaptive Immune Systems

Of the two types of immune systems, innate and adaptive, higher vertebrates have both to fight against pathogens, while insects have the innate immune system as their sole line of physiological defense.

Innate immunity responds to exposure to pathogens or toxic substances with acquired (preexisting genetic) mechanisms, such as physical barriers (e.g. cuticle, mucous membranes, etc.), and cells and chemicals that neutralize toxins and pathogens. The innate immune system in higher vertebrates uses cellular effectors. Effectors are small molecules or proteins that alter biochemical processes in a cell. Humoral (body fluid) effectors consist of supplement system fractions, acute phase proteins, antimicrobial peptides (AMPs), natural antibodies, and the various cytokines that modulate immune response.

Innate immune system specificity is in part inherited, resulting from co-evolution of individual immune systems with myriad pathogens.
Adaptive, or acquired, immunity refers to specific immune reactions tailored to particular toxins or pathogens. These toxins or pathogens are known as antigens (antibody generators) or immunogens. Adaptive immunity in vertebrates implies the ability to remember specific pathogens and react with production of antibodies specific to each pathogen when an organism is exposed to the same pathogen more than once.

Immunosenescence

Barrier immunity refers to the cells and molecules that withstand pathogens on epithelial surfaces (i.e., outside the organism) while systemic immunity refers to the cells and molecules responsible for defending against pathogens that cross this barrier and therefore reside inside the organism. Systemic immunity in insects can be further categorized into two components: cellular and humoral. Most studies of the hemocytes (a cellular component of humoral) demonstrate decreased numbers as bees age or transition between temporal castes and one type of cellular reaction, known as encapsulation, has been shown to be reduced in older bees. Finally, fat body quantification has demonstrated stage-related reductions in this organ, which represents the major source of hemolymph (circulatory fluid) immune effector proteins. In correlation, inducible antimicrobial activity in the hemolymph, mostly produced by the fat body, also decreases with age. However, not all systemic immune aspects decrease with age. For example, the humoral phenoloxidase-based melanization response does not diminish with honeybee age. Thus, factors other than colony-level resource allocation may influence immune function in older bees.

The awareness that the nurse to forager transition is not absolute in honey bees has important significance for the study of immunosenescence reported here. First, foragers may revert to nurse-like physiology and behavior in response to demographic changes. Second, honey bee workers may also develop into long-lived, diutinus workers or ‘winter bees’ instead of transitioning to foragers. While workers in this state share many of the physiological and behavioral characteristics of nurses, they are likely distinct and are critical in temperate climates for overwintering when brood production halts. In the case of forager to nurse reversion, it has been shown that reversal of some aspects of systemic immunosenescence occurs. Immune function has not been studied in depth in diutinus bees. However, senescence-associated defects in the function of other physiological systems in forager bees can be forestalled for months by entry into this state. The nurse to forager transition is controlled by factors signaling the demographic need of the hive through effects at the level of the individual. At the physiological level, this appears to be mechanistically regulated by the Juvenile Hormone/Vitellogenin axis. Vitellogenin itself represents a protein at the intersection of nutritional status and molecular control of the physiological and behavioral changes associated with the nurse to forager transition. Induction of systemic immunosenescence and its reversal appear to be controlled in part by levels of this protein.

Immune Response

All immune responses involve a sequence of events that can be generally grouped into three stages: 1) recognition, 2) activation of signaling pathways and 3) cellular and humoral effector mechanisms aimed at eliminating pathogens. The immune response is triggered by the recognition process in which pathogen-associated molecular patterns (PAMPs) are identified by pattern recognition receptors (PRRs) in immune system cells. In response, different signaling pathways are activated, promoting synthesis of the effectors and receptors involved in the humoral and cellular immune response, as well as peptidoglycan recognition proteins (PGRP). PGRPs are a group of highly conserved pattern recognition receptors with at least one peptidoglycan recognition domain capable of recognizing the peptidoglycan component of the cell wall of bacteria.

Social Immunity

One characteristic of social insects in general, and of bees in particular, is their social life, sharing a nest. Nests usually contain food stores and a high density of individuals living in relative homeostasis. The nests of social insects are therefore attractive sites for the development of various infectious agents. However, social insects have developed social immunity that assists their innate immunity systems, which is characterized by cooperative behavior within a colony through different mechanisms, such as the following:

1) Social fever. Social fever results from bees generating additional heat in the nest. This mechanism is costly for healthy individuals but allows pathogen control in infected hosts. Raising the nest temperature favors the control of the pathogenic fungus.

2) Grooming. Grooming is the ability of bees to remove external parasites from their bodies by using their mandibles and legs. There are two types of grooming behavior, self-grooming and social grooming. Social grooming involves the collaboration of several individuals, but self-grooming is more common than social grooming. Colonies in which a high proportion of workers express this trait are more resistant to infestations by the mite Varroa destructor than colonies in which fewer members express it. Moreover, the vigor with which a colony’s workers carry out grooming is directly related to the number of mites they remove from their bodies. Grooming behavior is influenced by genetic factors for which the degree of expression varies between honey bee colonies of different races and stocks. In several studies, a gene (Neurexin) has been mapped and associated with this behavior.

3) Hygienic behavior. Hygienic behavior is the ability of worker bees to detect and remove diseased or parasitized brood (larvae and pupae) from comb cells. This is a two-step defense mechanism. First, workers uncap cells containing diseased or parasitized larvae or pupae and then remove them from the nest. This social behavior is a defense mechanism that helps to control the fungus A. apis (causal agent of chalkbrood), the bacterium Paenibacillus larvae (etiological agent of American foulbrood), and the mite V. destructor. Bees of different genotypes vary in the level of expression of this behavior. Hygienic behavior is influenced by a group of at least seven genes, meaning it has a more complex genetic coding than previously thought, and also appears to be inherited maternally.

4) Gathering and use of propolis. Bees collect propolis, resins of trees (mainly from conifers) that have antiseptic and antimicrobial properties. They use them essentially as a prophylactic measure. Propolis is used to coat the interior of brood cells or to mummify any invertebrates or small vertebrates that enter and die inside the colony, preventing or minimizing the development of pathogenic bacteria and fungi. In addition, the presence of certain types of propolis inside the colony can promote the expression of genes of the bee immune system.

5) Decreased contact between congeners. Individuals express this type of altruistic behavior when sick by moving away from the colony to die outside the brood nest.

6) Offspring cannibalism. In stressful situations that can cause brood death (e.g. lack of food, extreme temperatures), nurse bees usually cannibalize dead brood to prevent the development of pathogenic microorganisms such as A. apis. This mechanism also prevents loss of nutrients from the colony.

As a defense strategy, social immunity substantially lowers pressure on the innate immune system of individual bees, thus reducing the number of genes required for defense against infection. This may explain why the honey bee possesses just one-third of the recognition and immune effector signaling genes of a mosquito or fruit fly.

Transgenerational immune priming

Honey bee colonies depend on the reproductive output of their queens, which in turn is contingent on the care they receive from worker bees. Viral infections in queens can compromise their reproductive output, while viral infections in workers can inhibit the successful functioning of the colony and its ability to care for the queen. Transgenerational immune priming (TGIP) occurs when queens transfer immune-related compounds or immune elicitors to their offspring, enhancing the ability of subsequent generations to resist infections. These maternal effects on offspring could positively impact colony health and resilience to viral infections. Some test results have shown that virus-challenged queens upregulated immune effectors in their eggs and ovaries. In contrast, naturally infected queens from field surveys did not; there were no significant differences in egg protein, lipid, or metabolite composition related to maternal viral load or ovary size. However, egg collection date strongly influenced the protein, lipid, and metabolite composition of eggs, potentially reflecting seasonal variations in pollen resources. These findings suggest that while viral infections can induce transgenerational effects on egg proteomes under short-term testing conditions, such effects are less apparent in natural settings and can be overshadowed by seasonal and other ecological factors.

Royal Jelly and Phenolic Acid

It all comes down to the food. After birth, if the worker bees determine that a new queen is needed, they pick one of the larvae and feed it royal jelly instead of pollen and honey like all worker bees and drones. Royal jelly is known as bee milk. It looks like “white snot” and is made of mostly water with combinations and sugars. It is secreted by the heads of worker bees.

Royal jelly is different than regular jelly, pollen, and honey of the worker bees because it has a different ration of mandibular to hypopharyngeal gland secretion. This means that it has no detectable trace of phenolic acid, which comes the flavonoids in the from the plant products eaten by regular worker bees. These flavonoids increase the immune responses (immune priming) of adult worker bees in regular pollen and jelly, which allows for them to have a strong immune response and work for long periods of time while the queen lack this. This also helps worker bees detoxify pesticides faster. Royal jelly also has an enzyme that inhibits the protein DMT 1 methyltransferase, which demethylates (removes one or more methyl groups from a molecule, especially from a biologically active molecule) an entire subset of genes in the larvae, allowing for it to develop into a queen. This also allows for the development of chemical protection of the queen’s ovaries, sheltering the toxic or metabolic effects of plant chemicals. This then allows the queen to remain fertile while leaving the worker bees sterile. This decision is made upon the first feeding so the queen would never be fed pollen as a larva and damage her immune system.

One would think that feeding the larvae royal jelly is what makes it into a queen; but rather, is the nutritional castration of withholding royal jelly from the worker bees that makes her the queen by isolating her. Royal jelly diminishes the toxic effects of pollen and honey on the reproductive system.

Pathogen Pressure

Honey bees display temporal polyethism, which is an age-driven division of labor. Younger adult bees remain in the hive and tend to developing brood, while older adult bees forage for pollen and nectar to feed the colony. As honey bees mature, the types of pathogens they experience also change. As such, pathogen pressure may affect bees differently throughout their lifespan.

While investigating immune strength across four developmental stages (larvae, pupae, nurses (1-day-old adults), and foragers (22–30 days old adults)) immune strength was most vigorous in older, foraging bees and weakest in young bees. Importantly, it was found that adult honey bees do not abandon cellular immunocompetence as has been proposed. In immunology, immunocompetence (IC) is the ability of the body to produce a normal immune response following exposure to an antigen. Induced shifts in behavioral roles may increase a colony’s susceptibility to disease if nurses begin foraging activity prematurely.

Variation in pathogen-specific selective pressure may result in IC dissimilarities across developmental stages. It’s hypothesized that selection has maximized disease resistance abilities at each developmental stage. Given that brood (larvae and pupae) are confined within a comb cell, they are limited in their ability to move away from approaching parasites or to otherwise avoid pathogens through behavioral mechanisms. As such, brood likely rely on cellular and humoral mechanisms of defense. Alternatively, adult honey bees display a range of hygienic and antipathogenic behaviors including grooming and removal of infected nestmates. Adult behavior is influenced by age, through an ontogenetic process termed temporal polyethism. During this progression, young adults (“nurse bees”) feed larvae until they develop into pupae, which are capped with wax and isolated until emergence as nurse bees. Nurses typically remain in the hive and perform hygienic activities and tend to the brood, while older adult bees (i.e. foragers) leave the hive to collect pollen and nectar.

Queen Quality

While the queen may be inherently better equipped with individual immune defenses, especially protecting her reproductive organs she is also generally protected from pathogens by several social immune mechanisms like grooming by her retinue of nurse bees, the secretion of antimicrobial substances in royal jelly, and the isolation within the hive, she is not entirely immune to infections. Viruses that infect honey bees have evolved strategies to also infect queens horizontally through worker contact and vertically through mating. Thus, most of the pathogens that infect workers can also be found in queens, however most infections appear to be innocuous with no overt symptomology. While it’s true that some pathogens have been linked with colony loss, the direct effects on queen health and immunity responses are far less understood. Among the viruses that infect queens, Deformed Wing Virus (DWV) is the most widespread and well-known. In the absence of the varroa mite (Varroa destructor) DWV normally persists at low levels within a colony with no apparent detrimental effects. It can be found in all life stages and castes, including glandular secretions used to feed developing larvae and members of the hive. When Varroa is abundant, there is a dramatic rise in DWV, which is aided in transmission by being directly injected into worker and drone hemolymph during feeding. While Varroa do not feed directly on the queen, high mite populations can cause high DWV viral levels in queen tissues. The combination of high viral levels and Varroa load is linked to the suppression of the immune response in workers, with the number of workers with overt symptomology (deformed/crippled wings) serving as a predictive marker for colony loss.

Queen Failure

As the sole reproductive female in a colony of thousands of individuals, queens are the cornerstones of the colonies that they head. Understanding what factors impact their health and reproductive potential is therefore of great interest to the beekeeping industry, which provides pollination services valued annually in the billions of dollars globally. While queens can live for 5 years or more, beekeepers regularly replace queens at much younger ages, often after less than 1 year. It is still unclear, though, exactly what factors and in what combinations contribute to the symptoms of “queen problems” or poor reproductive output, which are regularly reported as one of the main perceived causes of colony loss in North America.

Queens mate over a short period of time with multiple drones at a few weeks of age and store the sperm they acquire for the rest of their lives. The remaining quality and quantity of this stored sperm is one determining factor of queen quality—if a queen lacks viable sperm with which to fertilize eggs, either because she did not obtain enough through mating, or because the remaining sperm is no longer viable, her productivity will decline. Sperm quality can be affected by abiotic factors (environmental), such as temperature stress and pesticide exposure. Additionally, the age of larvae that beekeepers graft when rearing new queens can impact the physiology and size of queens, with older larvae developing into worker-like queens, which impacts their future reproductive potential. Queens perceived by beekeepers as failing (exhibiting drone laying in worker cells or producing poor brood patterns) have been shown to have reduced sperm viability and they also have smaller ovaries compared to their healthy counterparts of similar age and in similar environments at the same time of year. Also, natural viral infection has been linked to queen problems in field operations, finding that beekeeper-identified failing queens had higher viral RNA copy numbers and that queens with higher viral RNA copy numbers, regardless of their performance status (healthy or failing), also had smaller ovaries.

Queen Banks

In modern agriculture, honey bee queen failure is repeatedly cited as one of the major reasons for yearly colony loss. It was discovered that the honey bee queen gut microbiota alters according to early social environment and is strongly tied to the identity of the queen breeder (colony or queen bank). Like human examples, this early life variation appears to set the trajectory for ecological succession associated with social assimilation and queen productivity. The high metabolic demand of natural colony assimilation is associated with less bacterial diversity, a smaller hindgut microbiome, and a downregulation of genes that control pathogens and oxidative stress. Queens placed in less social environments with low metabolic demand (queen banks) developed a gut microbiota that resembled much older queens that produce fewer eggs. The queens key reproductive role in the colony may rely in part on a gut microbiome shaped by social immunity and the early queen rearing environment.

Mated queens were placed into an active colony or a storage hive for multiple queens: a queen-bank. Feeding intensity, social context, and metabolic demand differed greatly between the two environments. The gene expression associated with oxidative stress and immunity and performed high-throughput sequencing of the queen gut microbiome across four alimentary tract niches was examined. Microbiota and gene expression in the queen hindgut differed by time, queen breeder source, and metabolic environment. In the ileum (final section of the digestive system), upregulation of most immune and oxidative stress genes occurred regardless of treatment conditions, suggesting post mating effects on gut gene expression. Counterintuitively, queens exposed to the more social colony environment contained significantly less bacterial diversity indicative of social immune factors shaping the queen’s microbiome. Queen bank queens resembled much older queens with decreased Alpha 2.1, greater abundance of Lactobacillus firm5 and Bifidobacterium in the hindgut, and significantly larger ileum microbiotas, dominated by blooms of Snodgrassella alvi. Combined with earlier findings, it was concluded that the queen gut microbiota experiences an extended period of microbial succession associated with queen breeder source, post mating development, and colony assimilation.

When confined to a queen bank, a queen’s behavior is in stark contrast to a queen in a fully functional colony setting. An established queen in a colony is a metabolic workhorse, converting resources gathered by the entire hive into rapid egg production. The queen is continuously surrounded by a retinue of nutrient-rich workers, exercising choice among the workers she permits to feed her via trophallaxis, the social transmission of nutrients and other factors. Banked queens are also attended and fed by nurse bees, but these queens do not lay eggs, have much lower metabolic demand, and have less choice concerning trophallaxis. It’s then hypothesized that these differences in metabolic demand and trophallactic choice affect early queen microbiota succession and host immunity.

Selective Consumers

In the colony environment, queens are constantly tended and fed by a retinue of nutrient-replete workers. Despite the social immune mechanisms of workers, queens are susceptible to worker viruses and Nosema spp.. The ability of the queen to distinguish worker health status and select a healthy nurse will affect the diversity and abundance of microbes introduced to the queen. Detailed observations suggest that the queen selects which member of the retinue she accepts food from, but the mechanism of choice is unknown. The queen bank treatment interferes with behavioral choice because queens are confined to small restrictive cages covered with screens. We found that the diversity of the mouthpart and hindgut microbiota increased significantly when queens were placed into queen banks suggesting differences in microbial exposure or mechanisms of social immunity associated with a limited social environment. Counterintuitively, an earlier study of queens younger than 2 weeks revealed that social isolation was associated with larger and more diverse gut microbiomes. Similarly, queens associated with the deficient social environment of the queen bank also showed increased microbiome size and diversity. Collectively, these results suggest that factors associated with the active colony environment shape the early queen microbiome. These may include social immunity, substances present in royal jelly fed to queens, host-generated mechanisms associated with immune priming, and exposure to a wide variety of worker-vectored strains of Bombella apis.

Queen Gut

The process of gut bacterial succession in queens reflects establishment patterns shaped by diet, social environment, development, and immune training/priming. Queen guts are populated by a core microbiota that is distinct from workers, includes many pioneer species, and undergoes long-term succession consistent with the much longer life expectancy of queen phenotypes. In addition to the ecological succession, the queen microbiome may alter proximally in conjunction with diet factors and host metabolism as occurs in other long-lived organisms. Study results suggest the occurrence of novel microbes abundant in early queen guts that may train the immune system. The queen’s unique physiology and reproductive role provides transmission potential for microbes that can withstand or proliferate in highly antioxidant and antimicrobial royal jelly. Regardless of the social environment, young newly mated queens were dominated by Alpha 2.1, a pioneer strain from Acetobacteraceae that is enriched in young queens but slowly depleted with age. The variation in gut microbiota attributable to queen breeder source was significant and, like human examples, appears to set the trajectory for ecological succession in the gut microbiota associated with post mating development and social assimilation. Considering the overlap in queen and worker physiology, evolution of the honey bee gut microbiome has likely been molded in part by intercaste conflict and cooperation among its members.

Referenced Material

Extracting Layens Honey Frames

The Old Beekeeper – The natural rhythms of the colony.

Pollen: Why do bees and humans want it?

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