To Immunity and Beyond: Exploring the immune system during spaceflight

After 5 decades of human presence in Space, we are finally getting a grasp on the consequences of space travel for the human body. In addition to changes in the nervous, cardiovascular, and respiratory system, blood shows major alterations, indicating that our blood-resident immune cells do not take kindly to hurtling through space. While the long-term consequences of these changes are yet to be explored, researchers are beginning to uncover the depths of the extraterrestrial impact on the body’s main defense system.

A short history of human Space physiology

Human space physiology is the field of science studying the adaptation of normal body functions in space. The reaction of the human body to space travel was a vital consideration before the first rocket was even designed. In fact, we came to understand this after World War I. Pilots at the time experienced respiratory problems during and post flight. If that could happen at some hundred meters away from Earth surface, what would happen thousands of miles away? In the following years, researchers were able to come up with solutions for pilots and – later –  for astronauts.

Soon after World War II, the USA, the (late) USSR and Europe founded their Space Agencies NASA, ROSCOSMOS and ESA respectively.  They initiated research related to the physiological adaptation to spaceflight on animals and humans, in Space and in simulations on Earth.  

The collaboration between ESA and NASA led to the creation of the Spacelab, a modular science package for use on Space Shuttle flights. 

As time passed, state space agencies from various countries such as Australia, Japan, China and India as well as private entities such as SpaceX and Blue Origin also showed interest in this field.

During all this time, the immune system has been a primary concern – nobody would like to get sick in space, right? 

Immune (dys)function in Space 

The last few decades of research indicate that the immune system is by no means agnostic to space travel. The NASA Integrative Immune Study has shed light on several aspects of human immune response in Space. Many different types of immune cells change, including a key player in our front line of defense: the macrophage. Macrophages are specialized cells involved in the detection and destruction of bacteria and other harmful organisms. Macrophages not only eliminate pathogens, they also clear out billions of dead cells every day and are responsible for the constant and balanced regeneration of the body’s cellular architecture.

Macrophages are partially compromised due to spaceflight. The longer the duration of spaceflight, the less functional our macrophages seem to be. Studies indicate that macrophages are capable of surviving and functioning in  low gravity. However, the process by which they differentiate, or mature from a less specialized cell to one distinct in form and function, seems to be more restricted than on Earth. Studies in Space and in simulations suggest that low gravity lays obstacles to several key steps of this “maturation” procedure. For instance, molecules guiding this process, such as the macrophage colony stimulating factor (M-CSF) and interleukins (IL) IL-3 and IL-6, were less potent in low gravity. This diminished macrophage maturation prevents the development of fully functional macrophages, thereby blunting the immune response to dangers like invading pathogens (Figure 1).

Figure 1: Macrophages in Space. Under the normal physiologic conditions of Earth, macrophages mature and differentiate to eradicate invading pathogens like viruses and bacteria. One way that they accomplish this eradication is via phagocytosis, or engulfment, of pathogenic threats. In Space, this maturation process is stunted, impairing the ability of macrophages to fight viruses and other pathogens.

In addition to changes in macrophages, other specialized immune cells, such as B cells and T lymphocytes, tend to become less active due to unknown changes in the bone marrow, the central immune organ where immune cells develop.

Together, macrophages and these B/T lymphocytes represent members of the two major arms of the immune system: the innate arm and the adaptive arm. Macrophages, and other members of the innate immune system, are the body’s first line of defense against pathogens; these innate cells launch generalized, non-specific attacks against foreign entities in the body, from bacteria to allergens. B and T lymphocytes, which compose the adaptive immune system, are much more specialized — using tools like antibodies, they specifically attack particular pathogens, often leading to potent eradication of the infection.

Supposing that the immune system acts as a corporal police, the macrophages will patrol the avenue and detect whatever is going wrong. They may spot a car trespassing the speed limit, a car crash, or a limousine driven by the mafia. Macrophages will sound the alarm, block the road, try to address the issue by their own means, and pass the word to specialized forces, the adaptive immune cells. 

In space, the immune system is not fully functional. Because of the dampened macrophage maturation, the patrol forces may fail to detect suspicious movement in the avenue. When they do manage to detect them and pass the word, the operating capacity of the specialized forces will also be low. The same applies to a torrent of messengers and mediators, cells and substances that respond to the activation of macrophages and help arrange the logistics of the B/T cell response. Therefore, bad things such as invading pathogens go undetected. Latent (sleeping) viruses such as herpes may be reactivated. Microorganisms, who normally coexist peacefully in our skin or our intestines may become harmful. That’s a serious problem for the astronauts stuck in space.

The impacts of Space immunity on astronaut health

As a matter of fact, astronauts in a prolonged mission to the moon would be exposed to both external pathogens such as drug resistant Escherichia coli strains and numerous internal pathogens that would escape the immune surveillance. Taking E.coli as an example, we come to realize that not only our immune system, but also bacteria tend to adapt to Space. A recent study conducted in the ISS revealed that E. coli bacteria grow differently in space, leading to changes that make it more difficult to treat by means of immunity and antibiotics. 

On top of that, herpes viruses tend to behave as enemies behind the gates for astronauts. According to a recent paper,  60% of astronauts during their stay at the ISS tested positive for at least one herpes virus. This is an intriguing finding, because on Earth, herpes remains dormant unless the immunity of an individual is greatly impaired. Although astronauts have been extensively tested before flight to make sure that they are physically and mentally healthy, the activation of herpes on board adds additional evidence for the ways that spaceflight can impact immune function. This percentage is alarming if compared with people recently infected with herpes simplex virus 1 or 2 on Earth. Approximately one third of them sheds the virus. Such findings make prospective long-term space exploration missions, let alone space tourism, more complicated. On the other hand, the struggle against herpes viruses in Space may even give us clues to how to treat herpes infection more effectively in our terrestrial communities.

Besides astronauts’ susceptibility to pathogens, it is possible that immune deregulation may trigger inflammatory conditions. Joints can be easily damaged in Space due to gravity alterations. The body’s immune response to injury or infection results in immune cells flooding the problematic area in an attempt to clear any invading pathogens. Minor musculoskeletal damage occurring while moving in low gravity is followed by this influx of immune cells that causes the characteristic redness, tenderness, swelling, and pain known collectively as inflammation. Recent evidence suggests that in space, where adaptive and innate immunity do not function as they should, inflammation can grow out of control, leading to permanent damage of the joints, generally known as arthritis. Of course this process includes many more steps, but our understanding needs more time and studies to grow.

In any case, and particularly in space, we need to keep an eye on the bigger picture, which in this case is termed the space exposome. The space exposome consists of processes internal to the body, external exposures, and wider psychosocial factors at play in space. Internal processes such as the activation of macrophages and lymphocytes and their disrupted communication collide with external threats including not only infectious agents growing in space but also radiation, low gravity, dietary alterations, constant noise, and tricky hypo magnetic fields. The psychosocial terrain of spaceflight is harsh as well, including fear, a packed routine, and fragile interpersonal relations.

Explaining the space exposome in full is beyond our current understanding. However, space exploration goes on, so we must use the knowledge that we do have to protect astronauts as much as possible from the surprising immunological dangers of space travel.

Cover image: “Space Engine” by K-putt is licensed under CC BY-NC 2.0

Published by Christos Tsagkaris

Christos is studying Medicine at the University of Crete in Heraklion, Greece graduating in July 2021. He is affiliated with several scientific students associations and NGOs, including the Association of European Cancer Leagues,
the European Student Think Tank and #Students_Against_COVID and NovelMeds. He also serves as a health advocate at the EU level communicating cancer prevention messages and promoting the European Code Against Cancer. You can follow his writing in Twitter and Linkedin

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