Imagine sometime in the distant future we find and colonize an earth-like planet. Makes one wonder, will our immune system retain its capacity to protect us against possibly pathogenic bacteria from that planet? Gauthier et al in their Science Immunology paper set to test the limits of our immune cells using uncommon bacteria and found that a staggering 80% of them were immunosilent, i.e., they did not induce the expected reaction from immune cells.
To obtain obscure microbes (like bacteria from another planet), the researchers dived into the Pacific Ocean and collected bacteria from the depths of 200-3000m; a place where there is neither light nor mammalian life. Procuring bacteria from a remote ecological niche unexposed to any terrestrial life forms was pivotal for testing the limits of our immune cells; neither have deep-sea bacteria evolved in any way to bypass our defenses nor have we specially adapted to counter them.
The innate immune system is our body’s first line of defense which is non-specific and triggered by various foreign molecules. These immune cells can sense the invading bacteria and launch an inflammatory response in return, alerting the body about invaders. This sensing happens through Pattern Recognition Receptors (PRRs) that sense pathogen-associated molecular patterns which as the name suggests, are unique patterns found on pathogens. Toll-Like Receptors (TLRs), the most important family of PRRs sense everything from viral to bacterial particles like membrane components and genetic material of different kinds. There are 10 TLRs currently known to exist in humans and their discovery has also yielded a Nobel Prize to the scientists who pioneered their studies.
The researchers found that most bacterial samples they took from the Phoenix Islands Protected Area belonged to a gram-negative bacterial genus called Moritella. Hence, TLR4 was the focus of this study since it senses endotoxins found on gram-negative bacteria. One such endotoxin is Lipopolysaccharide (LPS)- a complex molecule made of lipids and polysaccharides- found in the outer membrane of bacteria. LPS is one of the most immunogenic parts of a bacteria and is crucial for priming an immune response. Scientists used the whole bacterium with intact LPS or isolated LPS to test the immune response but no inflammatory reaction from immune cells of mice and humans was detected in immunosilent strains. They also injected the bacteria into living mice and checked inflammatory cytokine levels but found no increase in the case of immunosilent strains.
So, what makes LPS from these immunosilent strains of Moritella so different? Lipid A is the part of the LPS molecule that interacts with TLR4 and is made of sugars bound to fatty acid chains. Through analytical methods like mass spectrometry, the researchers found that in the immunosilent strains, the size of fatty acid chains was much longer than in normal bacteria. The immunosilent strains carry much longer chains of 16 carbons as compared to immunostimulatory strains’ chains of 12-14 carbon length that are optimal for detection. Moreover, the immunosilent strains accommodate distinct enzymes involved in the biosynthesis of lipid A.
On the other hand, this interesting study display the efficiency of the mammalian defense system wherein despite being completely foreign to our normal environment, the immune system could sense and respond to some of the deep-sea bacteria. One of the main takeaways of this research is that although our innate immune system can sense most of the bacterial particles that exist, it has its limitations especially when abstract environments are concerned.
This research opens a previously unexplored area. What are the biological roles of this 16-carbon containing immunosilent LPS molecules? Can they be applied in silencing the immune system of patients with hyperreactive immunity (autoimmunity/allergy)? Can our immune system adapt to these bacteria if exposed to them? Can there be other antigens of the bacteria that can evade our immune system? We may not have a complete understanding of the defense against bacteria from largely foreign locations yet, but it is surprising how well our immune system has evolved that it can still sense bacteria from thousands of meters below sea level. This optimizes our future space endeavors.
Source: Anna E. Gauthier et al.; Deep-sea microbes as tools to refine the rules of innate immune pattern recognition; Science Immunology 2021.
Article author: Kevin Merchant. Kevin is a MS student at LMU Munich, Germany, who is passionate about Immunology and writing. He aims to simplify latest research so that it becomes accessible to all.
Editor: Sutonuka Bhar. Sutonuka is a PhD candidate at the University of Florida. Her work focuses on host immune responses against viruses and bacterial membrane vesicles.
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