**1. Introduction**

Since Yuri Gagarin became the first human to leave the Earth's confines in 1961, more and more humans have traveled into space, and manned space stations have been built. During spaceflights, the organism is subjected to a variety of chronic and acute stressors. The first category comprises factors such as microgravity, confinement, isolation, radiation, and disturbed circadian rhythm. The second category covers periods of intense activity, such as spacewalks, but also hypergravity exposure during takeoff and landing. While acute stressors have been described as beneficial to the host as they can mobilize individual's defense capacities, several studies have shown that chronic stress has deleterious effects, as it contributes to the weakening of the immune system and the development of pathologies such as inflammatory disease, infections, and cancers [1–5]. In that context, it is interesting to note that 15 of the 29 astronauts involved in the Apollo missions developed bacterial or viral infections during, immediately after, or within a week of landing [6]. In addition, the very first epidemiological study based on medical data collected from 46 astronauts who spent 6 months on the ISS showed that 46% of them exhibited significant immunological problems [7]. Among notable events, 40% were classified as rashes/hypersensitivities and 27% as infectious diseases. Taken together,

these data show that spaceflight-associated stressors affect, on average, the immune system of one out of two astronauts. Furthermore, these data demonstrate that immune system dysregulation occurs not only after landing but also during the flight [7].

In parallel of this immunological weakening, it is important to keep in mind that changes in microbial growth and pathogenicity have been observed [8, 9]. Depending on the bacteria studied, increased or decreased virulence [10, 11], altered sensitivity to antibiotics [12, 13], and/or increased biofilm formation [11, 13, 14] have been described as a result of the modulation of gene expression [9–11, 15, 16]. Moreover, there is some evidence to suggest that antibiotics may be less effective in space [12, 17, 18].

These microbial changes, combined with dysregulation of the immune system, certainly contribute to explain the increased susceptibility to infections observed in astronauts [19] (**Figure 1**). It is also noteworthy to keep in mind that, as the duration of space missions will increase, the potential for infectious diseases to arise during flight may become a critical issue because the probability of




**37**

*Spaceflight-Associated Immune System Modifications DOI: http://dx.doi.org/10.5772/intechopen.88880*

cross-contamination between crewmembers will increase. Additionally, microbial mutation rates may increase. Solar and cosmic radiation met during space missions, with a cumulative dose obviously increasing with mission duration, could contribute to the appearance of mutations potentially associated to resistance or diseases

Thus, caution should be paid to precisely understand how the immune system adapts, is modified/hampered, by unique environmental changes encountered during spaceflight. This knowledge is mandatory to allow the development of efficient biomedical strategies to preserve astronauts' heath during prolonged deep space exploration missions. In this chapter, we will review how spatial conditions affect the maturation of immune cells as well as the functions of mature immune cells

Cells that make up our immune system are derived from hematopoietic stem cells (HSC). These HSC will give rise to common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs). After several differentiation steps, CMPs will give raise to myeloid cells (granulocytes, monocytes, macrophages, and dendritic cells) and CLPs to lymphoid cells (B and T lymphocytes and NK cells). All

A number of studies have analyzed the impact of spaceflight on the development of cells belonging to the myeloid lineage (or myelopoiesis). A decrease in the number of granulocyte and monocyte progenitors in rodents that have been in space or subjected to anti-orthostatic suspension (a model commonly used in the laboratory to reproduce many of the physiological changes observed in flight) has

confirmed the inhibitory effect of microgravity on erythropoiesis (red blood cell production) [22]. Other studies have shown that the stressors encountered during spaceflight impact lymphocyte development (or lymphopoiesis). Diverse animal models have been used to address this question, such as mouse or the Iberian ribbed newt (*Pleurodeles waltl*, a urodele amphibian). The latter lends itself well to the constraints associated with space experiments and has all the cardinal elements of the mammalian immune system [23]. It has notably been observed that *P. waltl* larvae developed on board the ISS exhibit changes in the expression of IgM heavy-chain transcripts as well as a disruption in the expression of the Ikaros gene encoding transcription factors required for lymphopoiesis, suggesting that the latter could be weakened under spatial conditions [24]. This hypothesis was then confirmed in mice subjected to 21 days of anti-orthostatic suspension, which corresponds to a long-term mission at the human scale. It has been shown that this model induces a decrease in the number of CLPs and cells at the pro-B, pre-B, immature B, and mature B stages in the femoral bone marrow of suspended mice compared to control mice [25]. Furthermore, various causes of this weakening have been identified, such as a decrease in signal transduction by the interleukin-7 receptor and a decrease in the expression of transcription factors essential for B-cell development within the bone marrow. It has also been noted that this decrease in B lymphopoiesis is coupled with the remodeling of the bone tissue induced by the suspension, thereby reminding that all physiological systems interact within an organism and that these interactions have to be taken into account when analyzing the impact of stressors such as modeled microgravity. Finally, this sensitivity of hematopoiesis and the link with bone remodeling was confirmed in mice embarked on board the BION-M1 satellite for 30 days [26]. A decrease by a factor of two in the number of

progenitors in flight has

during such long and stressful endeavor as interplanetary missions.

required for the effective protection of the individual.

**2. Effects on the maturation of immune cells**

of these cells are involved in natural and/or specific immunity.

been demonstrated [20, 21]. The culture of human CD34+

#### **Figure 1.**

*Environmental changes associated with spaceflight (stressors) such as gravity change, the perturbation of the circadian rhythm (every day the residents of the ISS witness 16 sunrises and 16 sunsets), confinement, increased radiation, sleep deprivation, and nutritional factors weaken the immune system of about 50% of the astronauts. Most frequent immune changes consist in viral reactivations and lower responses of T and natural killer (NK) cells. These changes could be due to changes in cytokine expression and increased levels of stress hormones. In parallel, spaceflight environment might increase the virulence, resistance, and proliferation of some pathogens.*

*Spaceflight-Associated Immune System Modifications DOI: http://dx.doi.org/10.5772/intechopen.88880*

*Beyond LEO - Human Health Issues for Deep Space Exploration*

flight [7].

space [12, 17, 18].

these data show that spaceflight-associated stressors affect, on average, the immune system of one out of two astronauts. Furthermore, these data demonstrate that immune system dysregulation occurs not only after landing but also during the

In parallel of this immunological weakening, it is important to keep in mind that changes in microbial growth and pathogenicity have been observed [8, 9]. Depending on the bacteria studied, increased or decreased virulence [10, 11], altered sensitivity to antibiotics [12, 13], and/or increased biofilm formation [11, 13, 14] have been described as a result of the modulation of gene expression [9–11, 15, 16]. Moreover, there is some evidence to suggest that antibiotics may be less effective in

These microbial changes, combined with dysregulation of the immune system, certainly contribute to explain the increased susceptibility to infections observed in astronauts [19] (**Figure 1**). It is also noteworthy to keep in mind that, as the duration of space missions will increase, the potential for infectious diseases to arise during flight may become a critical issue because the probability of

*Environmental changes associated with spaceflight (stressors) such as gravity change, the perturbation of the circadian rhythm (every day the residents of the ISS witness 16 sunrises and 16 sunsets), confinement, increased radiation, sleep deprivation, and nutritional factors weaken the immune system of about 50% of the astronauts. Most frequent immune changes consist in viral reactivations and lower responses of T and natural killer (NK) cells. These changes could be due to changes in cytokine expression and increased levels of stress hormones. In parallel, spaceflight environment might increase the virulence, resistance, and proliferation of* 

**36**

**Figure 1.**

*some pathogens.*

cross-contamination between crewmembers will increase. Additionally, microbial mutation rates may increase. Solar and cosmic radiation met during space missions, with a cumulative dose obviously increasing with mission duration, could contribute to the appearance of mutations potentially associated to resistance or diseases during such long and stressful endeavor as interplanetary missions.

Thus, caution should be paid to precisely understand how the immune system adapts, is modified/hampered, by unique environmental changes encountered during spaceflight. This knowledge is mandatory to allow the development of efficient biomedical strategies to preserve astronauts' heath during prolonged deep space exploration missions. In this chapter, we will review how spatial conditions affect the maturation of immune cells as well as the functions of mature immune cells required for the effective protection of the individual.
